Optometry and Vision Sciences - Research Publications

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Author: Vingrys, Algis × Author: Jobling, Andrew × Subject: Vision ×

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    Susceptibility of Streptozotocin-Induced Diabetic Rat Retinal Function and Ocular Blood Flow to Acute Intraocular Pressure Challenge
    Wong, VHY ; Vingrys, AJ ; Jobling, AI ; Bui, BV (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-03)
    PURPOSE: To consider the hypothesis that streptozotocin (STZ)-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute IOP challenge. METHODS: Retinal function (electroretinogram [ERG]) was measured during acute IOP challenge (10100 mm Hg, increments of 5 mm Hg, 3 minutes per step, vitreal cannulation) in adult Long-Evans rats (6 weeks old; citrate: n = 6, STZ: n = 10) 4 weeks after citrate buffer or STZ (65 mg/kg, blood glucose >15 mM) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd x s x m(-2)) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry; citrate: n = 6, STZ: n = 10) was also measured during acute IOP challenge. Retinas were isolated for quantitative PCR analysis of nitric oxide synthase mRNA expression (endothelial, eNos; inducible, iNos; neuronal, nNos). RESULTS: STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mm Hg versus citrate: 67.5, CI: 62.1-72.4 mm Hg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mm Hg versus citrate: 65.1, CI: 61.9-68.6 mm Hg) and ocular blood flow (43.9, CI: 40.8-46.8 versus citrate: 53.4, CI: 50.7-56.1 mm Hg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P < 0.03). No difference was observed for iNos or nNos (P > 0.05) following IOP elevation. CONCLUSIONS: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNos expression and to autoregulate blood flow in response to stress.
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    Increased Susceptibility to Injury in Older Eyes
    Charng, J ; Nguyen, CTO ; Vingrys, AJ ; Jobling, AI ; Bui, BV (LIPPINCOTT WILLIAMS & WILKINS, 2013-03)
    PURPOSE: To determine whether there is an age-dependent susceptibility in retinal function in response to repeated anterior chamber cannulation with or without intraocular pressure (IOP) elevation. METHODS: Baseline electroretinograms were measured in 3- and 18-month-old Sprague-Dawley rats (n = 16 each group). Following baseline assessment, eyes were randomly assigned to undergo a 60-min anterior chamber cannulation with IOP either left at baseline (sham, 15 mm Hg) or elevated to 60 mm Hg. This was repeated three additional times, with each episode separated by 1 week. At weeks 1 to 3, dark-adapted retinal function was assessed immediately before cannulation, with final functional assessment at week 4. RESULTS: Both sham and IOP elevated eyes of older rats showed retinal dysfunction, which became more pronounced with the number of repeated insults. This effect was largest for responses arising from the inner retina. Repeated insult in younger eyes did not produce a change in amplitude but an increase in the sensitivity to light of photoreceptoral and bipolar cell components of the electroretinogram. CONCLUSIONS: Repeated trauma, not IOP, produces permanent retinal dysfunction in older eyes. Younger eyes appear to be able to withstand this type of injury by upregulating sensitivity of outer and middle retinal responses to maintain normal inner retinal function.