Dr. McLellan is a Board Certified veterinary ophthalmologist, an Associate Scientist in the Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, and a Clinical Instructor in the School of Veterinary Medicine, University of Wisconsin-Madison. Her NIH-funded research characterizes the genetic basis, clinical progression and pathological features of a spontaneous feline model of glaucoma. Dr. McLellan has experience with retinal imaging, aqueous humor dynamics, electrophysiology, and ocular histopathology in a range of laboratory animal species. She recently co-authored a textbook on comparative ocular pathology with Drs. Albert and Dubielzig.
Evoked potentials as a biomarker of remyelination.
Proc Natl Acad Sci U S A. 2019 Dec 16;:
Authors: Heidari M, Radcliff AB, McLellan GJ, Ver Hoeve JN, Chan K, Kiland JA, Keuler NS, August BK, Sebo D, Field AS, Duncan ID
Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.
PMID: 31843913 [PubMed - as supplied by publisher]
Genomic analysis for virulence determinants in feline herpesvirus type-1 isolates.
Virus Genes. 2019 Nov 27;:
Authors: Lewin AC, Coghill LM, McLellan GJ, Bentley E, Kousoulas KG
Feline herpesvirus type 1 (FHV-1) is a widespread cause of respiratory and ocular disease in domestic cats. A spectrum of disease severity is observed in host animals, but there has been limited prior investigation into viral genome factors which could be responsible. Stocks of FHV-1 were established from oropharyngeal swabs obtained from twenty-five cats with signs of infection housed in eight animal shelters around the USA. A standardized numerical host clinical disease severity scoring scheme was used for each cat from which an isolate was obtained. Illumina MiSeq was used to sequence the genome of each isolate. Genomic homogeneity among isolates was relatively high. A general linear model for fixed effects determined that only two synonymous single nucleotide polymorphisms across two genes (UL37/39) in the same isolate (from one host animal with a low disease severity score) were significantly associated (p ≤ 0.05) with assigned host respiratory and total disease severity score. No variants in any isolate were found to be significantly associated with assigned host ocular disease severity score. A concurrent analysis of missense mutations among the viral isolates identified three genes as being primarily involved in the observed genomic variation, but none were significantly associated with host disease severity scores. An ancestral state likelihood reconstruction was performed and determined that there was no evidence of a connection between host disease severity score and viral evolutionary state. We conclude from our results that the spectrum of host disease severity observed with FHV-1 is unlikely to be primarily related to viral genomic variations, and is instead due to host response and/or other factors.
PMID: 31776852 [PubMed - as supplied by publisher]
An Insight Into the Involvement of Mothers of Low Socioeconomic Status in Scottish Primary School Health Education Activities.
Health Educ Behav. 2019 Aug 28;:1090198119871329
Authors: Donnelly S, Buchan DS, Gibson AM, Mclellan G, Arthur R
School-based health activities that involve parents are more likely to be effective for child health and well-being than activities without a parent component. However, such school-based interventions tend to recruit the most motivated parents, and limited evidence exists surrounding the involvement of hard-to-reach parents with low socioeconomic status (SES). Mothers remain responsible for the majority of family care; therefore, this study investigated mothers with low SES to establish the reasons and barriers to their involvement in school-based health activities and to propose strategies to increase their involvement in those activities. Interviews were conducted with mothers with low SES, who were typically not involved in school-based health activities (n = 16). An inductive-deductive approach to hierarchical analysis revealed that there are several barriers resulting in mothers being less involved, particularly due to issues surrounding the schools' Parent Councils and the exclusivity of school-based events. Efforts made by the school to promote health activities and involve parents in such activities were revealed, alongside recommendations to improve on these practices. The findings offer multiple ways in which future school-based health interventions can recruit and involve mothers with low SES.
PMID: 31462107 [PubMed - as supplied by publisher]
Validation of the Icare® TONOVET plus rebound tonometer in normal rabbit eyes.
Exp Eye Res. 2019 Jun 12;:107698
Authors: Gloe S, Rothering A, Kiland JA, McLellan GJ
To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using each of the above four tonometers at manometric pressures ranging between 5 mmHg and 70 mmHg. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. A p-value of ≤0.05 was considered significant for all statistical tests. IOP values obtained with the TONOVET Plus (in 'lapine' mode) were significantly closer to manometric IOP than those obtained with the other tonometers tested. The TV01 (in 'd' dog setting) and Tono-Pen AVIA Vet™ were significantly more accurate compared to the Tono-Pen Vet™. All tonometers had high levels of precision, though the TONOVET Plus and TV01 were significantly more precise compared to the Tono-Pen AVIA Vet™. All tonometers tended to underestimate IOP, particularly at high pressures, however the TONOVET Plus was highly correlated with manometric IOP in the clinically relevant range of 5-50 mmHg. The TONOVET Plus is an appropriate choice of instrument for measuring IOP in rabbit eyes in both research and clinical settings.
PMID: 31201805 [PubMed - as supplied by publisher]
A comparison of physical activity from Actigraph GT3X+ accelerometers worn on the dominant and non-dominant wrist.
Clin Physiol Funct Imaging. 2018 Jul 30;:
Authors: Buchan DS, McSeveney F, McLellan G
The purpose of this study was to evaluate the agreement between several activity measures using raw acceleration data from accelerometers worn concurrently on the dominant and non-dominant wrist. Fifty-five adults (31·9 ± 9·7 years, 26 males) wore two ActiGraph GT3X+ monitors continuously for 1 day, one on their non-dominant wrist and the other on their dominant wrist. Paired t-tests were undertaken with sequential Holm-Bonferroni corrections to compare wear time, moderate-vigorous physical activity (MVPA), time spent in 10-min bouts of MVPA (MVPA10 min ) and the average magnitude of dynamic wrist acceleration (ENMO). Level of agreement between outcome variables from the wrists was examined using intraclass correlation coefficients (ICC, single measures, absolute agreement) with 95% confidence intervals and limits of agreement (LoA). Time spent across acceleration levels in 40 mg resolution were also examined. There were no significant differences between the non-dominant and dominant wrist for ENMO, wear time, MVPA or MVPA10 min . Agreement between wrists was strong for most outcomes (ICC ≥0·92) including wear time, ENMO, MVPA, MVPA10 min and the distribution of time across acceleration levels. Agreement was strong in the low acceleration bands (ICC = 0·970 and 0·922) with a mean bias of 3·08 min (LoA -55·18 to 61·34) and -5·43 (LoA -43·47 to 32·62). In summary, ENMO, MVPA, MVPA10 min , wear time and the distribution of time across acceleration levels compared well at the group level. The LOA from the two lowest acceleration levels suggest further work over a longer monitoring period is needed to determine whether outputs from each wrist are comparable.
PMID: 30058765 [PubMed - as supplied by publisher]
Relationship between corneal sensitivity, corneal thickness, corneal diameter, and intraocular pressure in normal cats and cats with congenital glaucoma.
Vet Ophthalmol. 2018 Mar 08;:
Authors: Telle MR, Chen N, Shinsako D, Kiland JA, Oikawa K, Møller Trane R, McLellan GJ
OBJECTIVE: To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD).
ANIMALS AND PROCEDURES: Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet-Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months-3.5 years. All procedures complied with an Institutional Animal Care and Use Committee-approved protocol. Data were analyzed by linear regression: paired Student's t tests for between-eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini-Hochberg adjusted for multiple comparisons, P-values < 0.05 were considered significant.
RESULTS: Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = -0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models.
CONCLUSIONS: Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma.
PMID: 29517120 [PubMed - as supplied by publisher]
The post-natal development of intraocular pressure in normal domestic cats (Felis catus) and in feline congenital glaucoma.
Exp Eye Res. 2017 Oct 17;166:70-73
Authors: Adelman S, Shinsako D, Kiland JA, Yaccarino V, Ellinwood NM, Ben-Shlomo G, McLellan GJ
Intraocular pressure (IOP) is the most consistent risk factor for progressive vision loss in glaucoma. Cats with recessively inherited feline congenital glaucoma (FCG) exhibit elevated IOP with gradual, painless progression of glaucoma similar to humans and are studied as a model of glaucoma in humans and animals. Here, post-natal development of IOP was characterized in normal domestic cats and in cats with FCG caused by a homozygous LTBP2 mutation. Rebound tonometry (TonoVet(®), ICare Oy, Finland) was used to measure IOP non-invasively, 2-3 times weekly in 63 FCG and 33 normal kittens, of both sexes, from eyelid opening until 3-6 months of age. IOPs in the left and right eyes of both FCG and normal kittens were compared by paired t-test and linear regression. One-way ANOVA and Tukey-Kramer post-tests were used to compare IOP of cats grouped by age and disease status. A p-value <0.05 was considered significant. In the second week of life, mean IOP was 7.16 mmHg (SD = 1.3) in normal kittens and 8.72 mmHg (SD = 1.4) in kittens with FCG. Mean IOP at age 10 weeks was significantly higher in FCG (19.8 mmHg; 95% CI = 17.7, 21.9 mmHg) than in normal kittens (13.2 mmHg; 95% CI = 11.9, 14.5 mmHg). At 3 months of age, IOP in normal cats reached adult values while IOP in FCG cats continued to increase through at least six months of age. These results provide ranges for normal IOP values in young kittens and confirm that IOP is significantly higher than normal by 10wks of age in this spontaneous feline glaucoma model.
PMID: 29054387 [PubMed - as supplied by publisher]
Tonometer validation and intraocular pressure reference values in the normal chinchilla (Chinchilla lanigera).
Vet Ophthalmol. 2017 Mar 17;:
Authors: Snyder KC, Lewin AC, Mans C, McLellan GJ
OBJECTIVES: To determine accuracy and precision of three commonly used tonometers (TonoVet(®) and TonoLab(®) (ICare Oy, Finland)-rebound tonometers, and Tono-Pen VET™ (Reichert, NY)-applanation tonometer) in normal chinchillas, and to establish a normal intraocular pressure (IOP) reference range in this species.
METHODS: The anterior chambers of three chinchilla eyes were cannulated ex vivo and readings obtained at manometric IOPs from 5 to 80 mmHg, using each of the three tonometers in random order. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. Tonometry was performed in both eyes of 60 chinchillas (age 8 weeks-16.2 years) using the TonoVet(®) and relationship between age and IOP analyzed using linear regression. For all statistical tests, P < 0.05 was significant.
RESULTS: Intraocular pressure values obtained using the Tono-Pen VET™ and TonoVet(®) (in dog calibration mode;'d') showed strong linear correlation with manometry within the physiologic and clinically relevant range of IOP (0-50 mmHg). The TonoVet(®) 'd' setting displayed significantly greater precision over the full range of IOP evaluated than the Tono-Pen VET™, and both TonoVet and Tono-Pen VET™ were significantly more accurate than the TonoLab(®) tonometer. Mean ± SD IOP (TonoVet(®) 'd') in chinchillas was 9.7 ± 2.5 mmHg, and the 95% reference interval was 4.7-14.7 mmHg.
CONCLUSIONS: Both the Tono-Pen VET™ and TonoVet(®) provided clinically acceptable estimates of IOP in chinchillas. The TonoVet(®) provides accurate and precise IOP values, while Tono-Pen VET™ derived measurements showed greater variability. Values obtained either with the TonoLab(®) or TonoVet(®) used in the 'unspecified' calibration setting were inaccurate in this species.
PMID: 28303681 [PubMed - as supplied by publisher]
Diagnostic performance of Body Mass Index, Waist Circumference and the Waist-to-Height Ratio for identifying cardiometabolic risk in Scottish pre-adolescents.
Ann Hum Biol. 2016 Nov 06;:1-6
Authors: Buchan DS, McLellan G, Donnelly S, Arthur R
BACKGROUND: Limited studies have examined the diagnostic performance of body mass index (BMI), waist circumference (WC) or waist-to-height ratio (WHtR) for identifying cardiometabolic risk (increased clustered glucose, triglycerides, mean arterial pressure and inv-HDL-cholesterol) in pre-adolescent youth.
AIM: To compare the utility of BMI, WC and WHtR as predictors of cardiometabolic risk (CMR) in Scottish pre-adolescent children.
SUBJECTS AND METHODS: A cross-sectional analysis of 223 Scottish children (55.2% boys, mean age =8.4 years) was undertaken. BMI, WC and WHtR were used as exposure variables within multivariate logistic regression analysis and ROC analysis to examine the utility of these anthropometrical indices in identifying those at cardiometabolic risk.
RESULTS: Individuals with an elevated WHtR, WC and BMI were 3.51 (95% CI = 1.71-7.23; p < .001); 2.34 (95% CI = 1.35-4.06; p = .002) and 2.59 (95% CI = 1.42-4.73; p = .002) times more likely to be at cardiometabolic risk, respectively. The areas under the curves [AUC] to identify children with cardiometabolic risk were significant and similar among anthropometric indices (AUC's = 0.60-0.65). When stratified by BMI, both WC and WHtR demonstrated a fair-to-good ability for identifying those at cardiometabolic risk (AUC = 0.75-0.81).
CONCLUSIONS: Findings suggest that the combination of BMI with either WC or WHtR may provide an added benefit in the assessment of cardiometabolic risk amongst pre-adolescents.
PMID: 27733066 [PubMed - as supplied by publisher]
Effects of topical corticosteroid administration on intraocular pressure in normal and glaucomatous cats.
Vet Ophthalmol. 2016 Feb 15;
Authors: Gosling AA, Kiland JA, Rutkowski LE, Hoefs A, Ellinwood NM, McLellan GJ
OBJECTIVE: The objective of this study was to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG).
ANIMALS STUDIED: Five normal and 11 FCG cats were studied in two cohorts.
PROCEDURES: IOP was measured by a single, masked observer, once daily, 3-5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; balanced salt solution (BSS) applied to the contralateral eye served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively.
RESULTS: A total of 8 of 11 FCG cats responded to topical CCS after 1-5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). Two of five normal cats responded to topical CCS with an appreciable, but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg).
CONCLUSIONS: Our data indicate that the incidence of steroid-induced IOP elevation in cats is lower than that of previously published feline studies. Cats with preexisting compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats.
PMID: 26876736 [PubMed - as supplied by publisher]
Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.
Stem Cells Transl Med. 2016 Feb;5(2):192-205
Authors: Becker S, Eastlake K, Jayaram H, Jones MF, Brown RA, McLellan GJ, Charteris DG, Khaw PT, Limb GA
Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance: Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection.
PMID: 26718648 [PubMed - in process]
Correction: A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus).
PLoS One. 2016;11(8):e0161517
Authors: Kuehn MH, Lipsett KA, Menotti-Raymond M, Whitmore SS, Scheetz TE, David VA, O'Brien SJ, Zhao Z, Jens JK, Snella EM, Ellinwood NM, McLellan GJ
[This corrects the article DOI: 10.1371/journal.pone.0154412.].
PMID: 27537365 [PubMed - as supplied by publisher]
A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus).
PLoS One. 2016;11(5):e0154412
Authors: Kuehn MH, Lipsett KA, Menotti-Raymond M, Whitmore SS, Scheetz TE, David VA, O'Brien SJ, Zhao Z, Jens JK, Snella EM, Ellinwood NM, McLellan GJ
The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linkage was established on cat chromosome B3 (LOD 18.38, θ = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG identifying a valuable animal model for primary glaucoma that closely resembles the human disease, providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.
PMID: 27149523 [PubMed - in process]
Validation of the TonoVet® rebound tonometer in normal and glaucomatous cats.
Vet Ophthalmol. 2013 Mar;16(2):111-8
Authors: McLellan GJ, Kemmerling JP, Kiland JA
Objective To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet(®) tonometer. Animals studied IOP readings obtained with the TonoVet(®) were compared to IOP readings determined by manometry and by the Tono-Pen XL(™) in 1 normal cat and two glaucomatous cats. TonoVet(®) and Tono-Pen XL(™) readings were also compared in a further six normal and nine glaucomatous cats. Procedures The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet(®) and Tono-Pen XL(™) . IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t-test. Results The TonoVet(®) was significantly more accurate than the Tono-Pen XL(™) (P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono-Pen XL(™) underestimated IOP when compared with the TonoVet(®) . Conclusions Both the TonoVet(®) and Tono-Pen XL(™) provide reproducible IOP measurements in cats; however, the TonoVet(®) provides readings much closer to the true IOP than the Tono-Pen XL(™) . The TonoVet(®) is superior in accuracy to the Tono-Pen XL(™) for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting.
PMID: 22672669 [PubMed - indexed for MEDLINE]
Oral vitamin E absorption in English Cocker Spaniels with familial vitamin E deficiency and retinal pigment epithelial dystrophy.
Vet Ophthalmol. 2012 Sep;15 Suppl 2:48-56
Authors: McLellan GJ, Bedford PG
BACKGROUND: Retinal Pigment Epithelial Dystrophy (RPED) with neuroaxonal degeneration in English Cocker Spaniels (ECS) is associated with systemic vitamin E deficiency in the absence of dietary insufficiency.
OBJECTIVE: To evaluate the ability of ECS with RPED to absorb orally administered vitamin E and establish a basis for vitamin E supplementation in affected dogs.
ANIMALS STUDIED: 8 RPED-affected ECS and five clinically normal dogs.
PROCEDURES: An oral vitamin E tolerance test (OVETT) was conducted in each dog. Blood samples were obtained prior to and at 3, 6, 9, 12, 24, 120, and 240 h following oral administration of 90 iu/kg of RRR-α-tocopherol. Plasma alpha tocopherol (αTOC) content was measured by normal phase, high-performance liquid chromatography, and indices of vitamin E absorption calculated.
RESULTS: There was marked variation in OVETT results between individuals. In RPED-affected ECS, mean peak plasma αTOC concentration (17.87 ± 13.21 μg/mL), attained after administration of a large oral dose of the vitamin, was significantly lower than the mean peak plasma αTOC concentration attained in normal dogs (47.61 ± 17.17 μg/mL; P < 0.005). However, the plasma concentrations achieved in 7/8 RPED-affected dogs remained within the normal reference range for plasma αTOC in vitamin E-replete dogs, for at least 12 h postdose.
CONCLUSIONS: Vitamin E-deficient ECS with RPED are capable of absorbing orally administered vitamin E. Twice daily administration of 600-900 iu tocopherol is likely to restore plasma vitamin E concentrations to the normal range in most affected dogs.
PMID: 22831287 [PubMed - indexed for MEDLINE]
Retinal intrinsic optical signals in a cat model of primary congenital glaucoma.
Invest Ophthalmol Vis Sci. 2012 Apr;53(4):1971-81
Authors: Schallek JB, McLellan GJ, Viswanathan S, Ts'o DY
PURPOSE: To examine the impact of reduced inner retinal function and breed on intrinsic optical signals in cats.
METHODS: Retinal intrinsic optical signals were recorded from anesthetized cats with a modified fundus camera. Near infrared light (NIR, 700-900 nm) was used to illuminate the retina while a charge-coupled device (CCD) camera captured the NIR reflectance of the retina. Visible stimuli (540 nm) evoked patterned changes in NIR retinal reflectance. NIR intrinsic signals were compared across three subject groups: two Siamese cats with primary congenital glaucoma (PCG), a control Siamese cat without glaucoma, and a control group of seven normally pigmented cats. Intraocular pressure (IOP), pattern electroretinogram, and optical coherence tomography measurements were evaluated to confirm the inner retinal deficit in PCG cats.
RESULTS: Stimulus-evoked, NIR retinal reflectance signals were observed in PCG cats despite severe degeneration of the nerve fiber layer and inner retinal function. The time course, spectral dependence, and spatial profile of signals imaged in PCG cats were similar to signals measured from normal and Siamese control cats.
CONCLUSIONS: Despite increased IOP, reduced nerve fiber layer thickness and ganglion cell function, intrinsic optical signals persist in cats affected with PCG. The mechanisms giving rise to intrinsic signals remain despite inner retinal damage. Signal strength was reduced in all Siamese cats compared to controls, suggesting that reduced intrinsic signals in PCG cats represent a difference between breeds rather than loss of ganglion cells. These results corroborated previous findings that retinal ganglion cells are not the dominant source of intrinsic optical signals of the retina.
PMID: 22395886 [PubMed - indexed for MEDLINE]
Effects of unilateral topical administration of 0.5% tropicamide on anterior segment morphology and intraocular pressure in normal cats and cats with primary congenital glaucoma.
Vet Ophthalmol. 2011 Sep;14 Suppl 1:75-83
Authors: Gomes FE, Bentley E, Lin TL, McLellan GJ
OBJECTIVE: To determine the effects of topical 0.5% tropicamide on anterior segment morphology (ASM) and intraocular pressure (IOP) in normal and glaucomatous cats. ANIMALS USED: Normal cats and cats with inherited primary congenital glaucoma (PCG).
PROCEDURES: Control IOP curves were performed in untreated normal and PCG cats. In the first experiment, tropicamide was applied OD in eight normal and nine PCG cats. IOP and pupillary diameter (PD) were measured at 0, 30, and 60 min, then hourly until 8 h post-treatment. In a second experiment, six normal and seven PCG cats received tropicamide OD. High-resolution ultrasound images were obtained at 0, 1, 5, and 10 h post-treatment to measure ASM changes. IOP and PD were measured OD at 0, 1, 2, 3, 5, 7, and 9 h.
RESULTS: In untreated normal cats IOP OU decreased throughout the day. In PCG cats IOP OU had wide fluctuations over time. In normal cats IOP response varied in the treated eye but did not change significantly in untreated eyes. IOP significantly increased from baseline in both eyes of all treated PCG cats. Increases in IOP were associated with some ASM changes. Cats with PCG had a significantly smaller angle recess areas, diminished ciliary clefts and decreased iris-lens contact. ASM changes were not strongly correlated with IOP in all cats.
CONCLUSIONS: The ASM of PCG cats is markedly different from normal cats, and clinically significant increases in IOP OU occur in cats with PCG after tropicamide treatment. The mechanism for this increase remains unclear.
PMID: 21923827 [PubMed - indexed for MEDLINE]
The effect of dorzolamide 2% on circadian intraocular pressure in cats with primary congenital glaucoma.
Vet Ophthalmol. 2011 Sep;14 Suppl 1:48-53
Authors: Sigle KJ, Camaño-Garcia G, Carriquiry AL, Betts DM, Kuehn MH, McLellan GJ
OBJECTIVE: To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats.
ANIMALS STUDIED: Seven adult cats with primary congenital glaucoma (PCG).
PROCEDURES: Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12-h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons.
RESULTS: Estimated mean IOP for the reference time point pre-treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2-6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU).
CONCLUSIONS: Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG.
PMID: 21923823 [PubMed - indexed for MEDLINE]
Removal of potentially confounding phenotypes from a Siamese-derived feline glaucoma breeding colony.
Comp Med. 2011 Jun;61(3):251-7
Authors: Rutz-Mendicino MM, Snella EM, Jens JK, Gandolfi B, Carlson SA, Kuehn MH, McLellan GJ, Ellinwood NM
Feline breeding colonies face genetic constraints involving founder effects. A Siamese-founded colony used to study primary congenital glaucoma displayed coat colors additional to the Siamese coat. Genes affecting pigment can exhibit pleiotropy on ocular development and function. To remove potentially confounding phenotypes from our colony, we documented the source and frequency of the Siamese allele at the gene for tyrosinase (TYR), the dilution allele at melanophilin (MLPH), and the brown allele at tyrosinase-related protein 1 (TYRP1). We used PCR-RFLP diagnostics to genotype cats in our colony for the published alleles. A commercially acquired phenotypically normal tom was the source of the dilute allele. A founding Siamese queen was the source of the brown allele. Founders also were blood-typed and screened for disease-associated alleles segregating in Siamese cats at 3 loci (ASB, GLB1, and CEP290). Siamese founders were normal at all loci except ASB, at which both animals carried the hypomorpic allele. Current stock is being managed to limit production of glaucomatous cats with brown, dilute, or Siamese phenotypes or homozygosity for the ASB hypomorphic allele. Genotyping will aid in the elimination of these alleles. The clinical effect of these phenotypes and alleles on the glaucoma phenotype is uncertain, but their elimination will remove potentially confounding effects. In conclusion, when founding a colony, stock should be selected or screened to limit potentially confounding phenotypes. When studying the immune, nervous, and visual systems, screening stock for alleles known to be associated with coat color may be warranted.
PMID: 21819695 [PubMed - indexed for MEDLINE]
A keratoprosthesis prototype for the dog.
Vet Ophthalmol. 2010 Jan;13(1):47-52
Authors: Allgoewer I, McLellan GJ, Agarwal S
OBJECTIVE: To describe the technique for implantation of a novel keratoprosthesis (KP) prototype and evaluate its application for the treatment of corneal blindness in dogs.
ANIMALS STUDIED: Seven dogs, all of them being clinically blind before surgery as a result of severe corneal endothelial disease (5/7) or chronic superficial keratitis (2/7) that were unresponsive to prior therapy.
PROCEDURES: A silicone KP was implanted unilaterally, just anterior to Descemet's membrane, after creating a stromal pocket by deep stromal lamellar dissection.
RESULTS: Implantation of the KP was accomplished without complication in six of seven operated dogs. In the remaining case, an intra-operative complication (perforation of Descemet's membrane) was associated with extrusion of the KP 8 weeks postoperatively. All operated eyes regained limited vision after surgery. Three to six months after implantation purulent keratitis occurred in all five eyes with endothelial disease, necessitating surgical removal of the KP 6 months postoperatively in 5/7 eyes.
CONCLUSIONS: This KP prototype shows promise as a treatment for certain blinding corneal diseases. However, changes in the design of this KP, allowing improved stromal integration, will be necessary before its clinical application can be approved.
PMID: 20149176 [PubMed - indexed for MEDLINE]