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 (10-100 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.s.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. (Invest Ophthalmol Vis Sci. 2013; 54: 2133-2141) DOI: 10.1167/iovs.13-11595

We recorded spike activity of single neurones in the middle temporal visual cortical area (MT or V5) of anaesthetised macaque monkeys. We used flashing, stationary spatially circumscribed, cone-isolating and luminance-modulated stimuli of uniform fields to assess the effects of signals originating from the long-, medium- or short- (S) wavelength-sensitive cone classes. Nearly half (41/86) of the tested MT neurones responded reliably to S-cone-isolating stimuli. Response amplitude in the majority of the neurones tested further (19/28) was significantly reduced, though not always completely abolished, during reversible inactivation of visuotopically corresponding regions of the ipsilateral primary visual cortex (striate cortex, area V1). Thus, the present data indicate that signals originating in S-cones reach area MT, either via V1 or via a pathway that does not go through area V1. We did not find a significant difference between the mean latencies of spike responses of MT neurones to signals that bypass V1 and those that do not; the considerable overlap we observed precludes the use of spike-response latency as a criterion to define the routes through which the signals reach MT.

PURPOSE. We demonstrated that eyes of young animals of various species (chick, tree shrew, marmoset, and rhesus macaque) can shorten in the axial dimension in response to myopic defocus.METHODS. Chicks wore positive or negative lenses over one eye for 3 days. Tree shrews were measured during recovery from induced myopia after 5 days of monocular deprivation for 1 to 9 days. Marmosets were measured during recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes, or from wearing positive lenses over one or both eyes. Rhesus macaques were measured after recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes. Axial length was measured with ultrasound biometry in all species.RESULTS. Tree shrew eyes showed a strong trend to shorten axially to compensate for myopic defocus. Of 34 eyes that recovered from deprivation-induced myopia for various durations, 30 eyes (88%) shortened, whereas only 7 fellow eyes shortened. In chicks, eyes wearing positive lenses reduced their rate of ocular elongation by two-thirds, including 38.5% of eyes in which the axial length became shorter than before. Evidence of axial shortening in rhesus macaque (40%) and marmoset (6%) eyes also occurred when exposed to myopic defocus, although much less frequently than that in eyes of tree shrews. The axial shortening was caused mostly by the reduction in vitreous chamber depth.CONCLUSIONS. Eyes of chick, tree shrew, marmoset, and rhesus macaque can shorten axially when presented with myopic defocus, whether the myopic defocus is created by wearing positive lenses, or is the result of axial elongation of the eye produced by prior negative lens wear or deprivation. This eye shortening facilitates compensation for the imposed myopia. Implications for human myopia control are significant.

Wong RC, Cloherty SL, Ibbotson MR, O' Brien BJ. Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis. J Neurophysiol 108: 2008-2023, 2012. First published July 11, 2012; doi: 10.1152/jn.01091.2011.-Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

Background: We consider whether pre-existing streptozotocin induced hyperglycemia in rats affects the ability of the eye to cope with a single episode of acute intraocular pressure (IOP) elevation. Methods: Electroretinogram (ERG) responses were measured (−6.08 to 1.92 log cd.s.m−2) in anaesthetized (60:5 mg/kg ketamine:xylazine) dark-adapted (>12 h) adult Sprague–Dawley rats 1 week after a single acute IOP elevation to 70 mmHg for 60 min. This was undertaken in rats treated 11 weeks earlier with streptozotocin (STZ, n012, 50 mg/kg at 6 weeks of age) or citrate buffer (n012). ERG responses were analyzed to derive an index of photoreceptor (a-wave), ON-bipolar (b-wave), amacrine (oscillatory potentials) and inner retinal (positive scotopic threshold response, pSTR) function. Results: One week following acute IOP elevation there was a significant reduction of the ganglion cell pSTR (−35± 11 %, P00.0161) in STZ-injected animals. In contrast the pSTR in citrate-injected animals was not significant changed (+16±14 %). The negative component of the STR was unaffected by IOP elevation in either citrate or STZ-treated groups. Photoreceptoral (a-wave, citratecontrol +4±3 %, STZ +4±5 %) and ON-bipolar cell (b-wave, control +4±3 %, STZ +4±5 %) mediated responses were not significantly affected by IOP elevation in either citrate- or STZ-injected rats. Finally, oscillatory potentials (citrate-control +8±23 %, STZ +1±17 %) were not reduced 1 week after IOP challenge. Conclusions: The ganglion cell dominated pSTR was reduced following a single episode of IOP elevation in STZ diabetic, but not control rats. These data indicate that hyperglycemia renders the inner retina more susceptible to IOP elevation.

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.

Purpose: To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice. Methods: IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure–function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (−4.54, −2.23, and 0.34 log cd • s • m−2) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike. Results: The pSTR was most sensitive to IOP elevation with 50% amplitude loss (μ) at 41 mm Hg (μ, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR (−30% ± 6%, P < 0.001) and OP (−27% ± 2%, P < 0.001) amplitudes were reduced, whereas other components were unaffected. Conclusions: The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP amplitude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike.

Purpose: The global or gross response index of visual performance measured from the eye does not necessarily translate to global responses measured from the brain. A better understanding of this relationship would facilitate the monitoring of disease models that affect the visual pathway. We consider whether rod- and cone-retino-cortical-pathways are equally affected by acute IOP elevation. Methods: Acute, stepwise IOP elevation (10, 30, 40, 50, 60, 70 mm Hg) was induced in anesthetized dark- (N = 8) and light-adapted pigmented rats (N = 6). Electroretinogram (ERG) and visual evoked potentials (VEP) were simultaneously measured after 10 minutes at each step. Relative amplitudes (treated/baseline, %) as a function of IOP level were described with a cumulative normal function. Results: Our results showed decline in scotopic and photopic ERGs with IOP elevation. Photopic ERG responses were less sensitive to IOP challenge than scotopic ERG responses. Despite significant reductions of ganglion cell–mediated waveforms at 70 mm Hg, the VEP showed only subtle decreases in amplitude. Intraocular pressure elevation produced similar effects on rod- and cone-mediated VEP waveforms. Conclusions: We show that cone signals are less sensitive than rod ERGs to acute IOP challenge. Also, retinal signals are more sensitive than are cortical signals to IOP stress, suggesting that cortical processing may act to salvage reductions expected from attenuated retinal output.

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 (10–100 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.s.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.

Retinal function is known to be more resistant than blood flow to acute reduction of ocular perfusion pressure (OPP). To understand the mechanisms underlying the disconnect between blood flow and neural function, a mathematical model is developed in this study, which proposes that increased oxygen extraction ratio compensates for relative ischemia to sustain retinal function. In addition, the model incorporates a term to account for a pressure-related mechanical stress on neurons when OPP reduction is achieved by intraocular pressure (IOP) elevation. We show that this model, combining ocular blood flow, oxygen extraction ratio, and IOP mechanical stress on neurons, accounts for retinal function over a wide range of OPP manipulations. The robustness of the model is tested against experimental data where ocular blood flow, oxygen tension, and retinal function were simultaneously measured during acute OPP manipulation. The model provides a basis for understanding the retinal hemodynamic responses to short-term OPP challenge.

Paying attention improves performance, but is this improvement regardless of what we attend to? We explored the differences in performance between attending to a location and attending to a feature when perceiving global motion. Attention was first cued to one of four locations that had coherently moving dots, while the remaining three had randomly moving distracter dots. Participants then viewed a colored display, wherein the color of the coherently moving dots was cued instead of location. In the third task, participants identified the location that had a particular cued direction of motion. Most observers reported reductions of motion threshold in all three tasks compared to when no cue was provided. However, the attentional bias generated by location cues was significantly larger than the bias resulting from feature cues of direction or color. This effect is consistent with the idea that attention is largely controlled by a fronto-parietal network where spatial relations are preferentially processed. On the other hand, color could not be used as a cue to focus attention and integrate motion. This finding suggests that color relies heavily on processing by ventral temporal cortical areas, which may have little control over the global motion areas in the dorsal part of the brain.

We recorded spike activity of single neurones in the middle temporal visual cortical area (MT or V5) of anaesthetised macaque monkeys. We used flashing, stationary spatially circumscribed, cone isolating and luminance modulated stimuli of uniform fields to assess the effects of signals originating from the long- (L), medium- (M) or short- (S) wavelength sensitive cone classes. Nearly half (41/86) of the tested MT neurones responded reliably to S-cone isolating stimuli. Response amplitude in the majority of the neurones tested further (19/28) was significantly reduced, though not always completely abolished, during reversible inactivation of visuotopically corresponding regions of the ipsilateral primary visual cortex (striate cortex, area V1). Thus, the present data indicate that signals originating in S-cones reach area MT, either via V1 or by a pathway that does not go through area V1. We did not find a significant difference between the mean latencies of spike responses of MT neurones to signals that bypass V1 and those that do not; the considerable overlap we observed precludes the use of spike-response latency as a criterion to define the routes through which the signals reach MT.