Dr. Kim is a Senior Scientist in the Department of Ophthalmology and Visual Sciences at the University of Wisconsin School of Medicine and Public Health. She is a visual psychophysicist with extensive training and experience in research neurophysiology and electrophysiology. She has worked with an array of vertebrate species in the investigation of retinal and subcortical function. She has specific background experience in the nonhuman and human aging visual systems and in nonhuman primate experimental glaucoma.
Effect of intraocular pressure (IOP), volume and location on the distribution of aqueous solutions injected into the suprachoroidal (SC) space
Investigative Ophthalmology & Visual Science, 63(7), pp.4152-F0144
Normative Values for Multifocal ERGs Recorded from Cynomolgus Macaques in a Non-clinical Setting
In Investigative Ophthalmology & Visual Science (Vol. 60, No. 9)
Variability in the Electroretinographic Response of Laboratory Animals
Investigative Ophthalmology & Visual Science, 57(12), pp.5766-5766
Functional and Structural Effects of Subretinal Dose Delivery in Mice
Investigative Ophthalmology & Visual Science, 56(7), pp.245-245
Regional choroidal blood flow and multifocal electroretinography in experimental glaucoma in rhesus macaques
Invest Ophthalmol Vis Sci. 2014 Nov 4;55(12):7786-98. doi: 10.1167/iovs.14-14527.
PURPOSE: To test a hypothesis of regional variation in the effect of experimental glaucoma on choroidal blood flow (ChBF) and retinal function.
METHODS: Five rhesus macaques underwent laser trabecular destruction (LTD) to induce elevated intraocular pressure (IOP). Intraocular pressures were elevated for 56 to 57 weeks. Multifocal electroretinographic (mfERG) and multifocal visual evoked cortical potential (mfVEP) testing were performed at regular intervals before and during the period of IOP elevation. At euthanasia, the IOP was manometrically controlled at 35 (experimentally glaucomatous eye) and 15 (fellow control eye) mm Hg. Fluorescent microspheres were injected into the left ventricle. Regional ChBF was determined.
RESULTS: All of the experimentally glaucomatous eyes exhibited supranormal first-order kernel (K1) root mean square (RMS) early portions of the mfERG waveforms and decreased amplitudes of the late waveforms. The supranormality was somewhat greater in the central macula. Second-order kernel, first slice (K2.1) RMS mfVEP response was inversely correlated (R(2) = 0.97) with axonal loss. Total ChBF was reduced in the experimentally glaucomatous eyes. The mean blood flow was 893 ± 123 and 481 ± 37 μL/min in the control and glaucomatous eyes, respectively. The ChBF showed regional variability with the greatest proportional decrement most often found in the central macula.
CONCLUSIONS: This is the first demonstration of globally reduced ChBF in chronic experimental glaucoma in the nonhuman primate. Both the alteration of mfERG waveform components associated with outer retinal function and the reduction in ChBF were greatest in the macula, suggesting that there may be a spatial colocalization between ChBF and some outer retinal effects in glaucoma.
PMID:25370515 | PMC:PMC4254281 | DOI:10.1167/iovs.14-14527
Gender Differences in Anesthetized Primate ERG and Full-field Flash VEP
Investigative Ophthalmology & Visual Science, 55(13), pp.5130-5130
Structural and functional effects of hemiretinal endodiathermy axotomy in cynomolgus macaques
Invest Ophthalmol Vis Sci. 2013 May 17;54(5):3479-92. doi: 10.1167/iovs.12-11265.
PURPOSE: Outer retinal injury has been well described in glaucoma. To better understand the source of this injury, we wanted to develop a reliable model of partial retinal ganglion cell (RGC) axotomy.
METHODS: Endodiathermy spots were placed along the inferior 180° adjacent to the optic nerve margin in the right eyes of four cynomolgus monkeys. Fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG) were performed at various intervals. Two animals were sacrificed at 3 months. Two animals were sacrificed at 4 months, at which time they underwent an injection of fluorescent microspheres to measure regional choroidal blood flow. Retinal immunohistochemistry for glial fibrillary acidic protein (GFAP), rhodopsin, S-cone opsin, and M/L-cone opsin were performed, as were axon counts of the optic nerves.
RESULTS: At 3 months, there was marked thinning of the inferior nerve fiber layer on SD-OCT. The mfERG waveforms were consistent with inner but not outer retinal injury. Greater than 95% reduction in axons was seen in the inferior optic nerves but no secondary degeneration superiorly. There was marked thinning of the nerve fiber and ganglion cell layers in the inferior retinas. However, the photoreceptor histology was similar in the axotomized and nonaxotomized areas. Regional choroidal blood flow was not affected by the axotomy.
CONCLUSIONS: Unlike experimental glaucoma, hemiretinal endodiathermy axotomy (HEA) of the RGCs produces no apparent anatomic, functional, or blood flow effects on the outer retina and choroid.
PMID:23620427 | PMC:PMC3658266 | DOI:10.1167/iovs.12-11265
Inner Nuclear Layer (INL) Cystoid Spaces (Lacunae) Observed in Experimental Glaucoma and Axotomy in Non-Human Primates (NHPs)
Investigative Ophthalmology & Visual Science, 54(15), pp.4818-4818
Electrophysiologic Correlates of RNFL Thickness in Experimental Glaucoma
Investigative Ophthalmology & Visual Science, 54(15), pp.794-794
Structure/function studies and the effects of memantine in monkeys with experimental glaucoma
Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2368-76. doi: 10.1167/iovs.11-8475.
Purpose. The scanning laser polarimetry with variable corneal compensation (GDx VCC) methodology was established and verified in monkeys with experimental glaucoma (ExpG). Terminal GDx parameters were correlated with axon counts and electrophysiologic measures. The effects of memantine on these parameters were investigated. Methods. ExpG was induced in monkeys and intraocular pressure monitored weekly. Some monkeys received memantine in their diet before and after ExpG induction (1-10 months). GDx VCC scans, stereophotographs, and multifocal visual evoked potential (mfVEP) data were collected at baseline and every 6 to 8 weeks until euthanasia. Optic nerves were prepared for axon counting and other morphologic analysis. Results. There was no difference in IOP elevation exposure between memantine-treated and no-memantine-treated monkeys. The percentage of the optic nerve area composed of connective tissue septa was significantly greater in ExpG eyes than in Fellow eyes. There was a strong positive correlation between axon counts and terminal GDx parameter measures. Animals not receiving memantine exhibited significantly lower mfVEP amplitudes in ExpG eyes compared with the ipsilateral baseline or the final value in the Fellow eye. ExpG eyes from memantine-treated animals had higher overall mean amplitudes that were not significantly different relative to the ipsilateral baseline and final amplitudes in the Fellow eye. Conclusions. The authors' studies confirm that GDx VCC can be utilized in monkey ExpG studies to detect early retinal structural changes and that these changes are highly correlated with optic nerve axon counts. These structural changes may or may not lead to central functional changes as shown by the mfVEP in response to investigational therapies.
PMID:22427549 | PMC:PMC3833458 | DOI:10.1167/iovs.11-8475
The effect of pentobarbital sodium and propofol anesthesia on multifocal electroretinograms in rhesus macaques
Doc Ophthalmol. 2012 Feb;124(1):59-72. doi: 10.1007/s10633-011-9306-x. Epub 2011 Dec 27.
We compared the suitability of pentobarbital sodium (PB) and propofol (PF) anesthetics for multifocal electroretinograms (mfERGs) in rhesus macaques. mfERGs were collected from 4 ocularly normal rhesus macaques. All animals were pre-anesthetized with intramuscular ketamine (10-15 mg/kg). Intravenous PB induction/maintenance levels were 15 mg/kg/2-10 mg/kg and for PF, 2-5 mg/kg/6-24 mg/kg/h. There were 3 testing sessions with PB anesthesia and 5-7 testing sessions with PF anesthesia. All PB sessions were carried out before PF. First-order (K1) and second-order (first slice) kernels (K2.1) response density amplitude (RDA), implicit time (IT), and root mean square signal-to-noise ratios (RMS SNR) of the low-frequency (LFC) and high-frequency (HFC) components were evaluated. The use of PF or PB anesthesia resulted in robust, replicable mfERGs in rhesus macaques; however, RMS SNR of K1 LFC in ring and quadrant analyses was significantly larger for PF than for PB. Additionally, K1 RDA under PF was significantly larger than under PB for N1, P1, and P2 components (ring and quadrant) and for N2 (quadrant). PF IT was significantly prolonged (<1 ms) relative to PB IT for N1, P1 (ring), and N1 (quadrant), while PB IT was significantly prolonged (0.8-4.2 ms) relative to PF IT for N2 and P2 (ring and quadrant). K1 HFC and K2.1 LFC did not differ significantly between PB and PF in the ring or quadrant analyses. The response differences found with PB and PF anesthesia likely arise from variable relative effects of the anesthetics on retinal γ-aminobutyric acid (GABA(A)) receptors, and in part, on glycine and on glutamate receptors. Given the advantages of a stable anesthetic plane with continuous intravenous infusion and a smoother, more rapid recovery, PF is an appealing alternative for mfERG testing in rhesus macaques.
PMID:22200766 | PMC:PMC3295608 | DOI:10.1007/s10633-011-9306-x
Functional and anatomic consequences of subretinal dosing in the cynomolgus macaque
Arch Ophthalmol. 2012 Jan;130(1):65-75. doi: 10.1001/archophthalmol.2011.295. Epub 2011 Sep 12.
OBJECTIVE: To characterize functional and anatomic sequelae of a bleb induced by subretinal injection.
METHODS: Subretinal injections (100 μL) of balanced salt solution were placed in the superotemporal macula of 1 eye in 3 cynomolgus macaques. Fellow eyes received intravitreal injections (100 μL) of balanced salt solution. Fundus photography, ocular coherence tomography, and multifocal electroretinography were performed before and immediately after injection and again at intervals up to 3 months postinjection. Histopathologic analyses included transmission electron microscopy and immunohistochemistry for glial fibrillary acidic protein, rhodopsin, M/L-cone opsin, and S-cone opsin.
RESULTS: Retinas were reattached by 2 days postinjection (seen by ocular coherence tomography). Multifocal electroretinography waveforms were suppressed post-subretinal injection within the subretinal injection bleb and, surprisingly, also in regions far peripheral to this area. Multifocal electroretinography amplitudes were nearly completely recovered by 90 days. The spectral-domain ocular coherence tomography inner segment-outer segment line had decreased reflectivity at 92 days. Glial fibrillary acidic protein and S-cone opsin staining were unaffected. Rhodopsin and M/L-cone opsins were partially displaced into the inner segments. Transmission electron microscopy revealed disorganization of the outer segment rod (but not cone) discs. At all postinjection intervals, eyes with intravitreal injection were similar to baseline.
CONCLUSIONS: Subretinal injection is a promising route for drug delivery to the eye. Three months post-subretinal injection, retinal function was nearly recovered, although reorganization of the outer segment rod disc remained disrupted. Understanding the functional and anatomic effects of subretinal injection is important for interpretation of the effects of compounds delivered to the subretinal space.
CLINICAL RELEVANCE: Subretinal injection is a new potential route for drug delivery to the eye. Separating drug effects from the procedural effects is critical.
PMID:21911651 | PMC:PMC3254795 | DOI:10.1001/archophthalmol.2011.295
Inter-ocular And Inter-subject Variability In The Full-field Electroretinograms Of Rabbits And Monkeys
Investigative Ophthalmology & Visual Science, 52(14), pp.703-703
Evaluation of EIAV Based Lentiviral Vectors Following Ocular Delivery in the Nonhuman Primate Model: Development of RetinoStat®
Investigative Ophthalmology & Visual Science, 49(13), pp.5340-5340
Standardized Full-Field Electroretinography in Cynomolgus Monkeys
Investigative Ophthalmology & Visual Science, 49(13), pp.5816-5816
Multifocal visual evoked potentials in the anesthetized non-human primate
Current eye research, 31(10), pp.885-893.
Measurement of regional choroidal blood flow in rabbits and monkeys using fluorescent microspheres
Archives of Ophthalmology, 124(6), pp.860-868.
Interspecies and gender differences in multifocal electroretinograms of cynomolgus and rhesus macaques
Documenta ophthalmologica, 109, pp.73-86.
VEP and PERG acuity in anesthetized young adult rhesus monkeys
Visual neuroscience, 16(4), pp.607-617.