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Purpose: To study the effect of intracameral injections of chondroitin sulfate (CS) on intraocular pressure (IOP), retinal function, and histology in rats., Methods: Acute or chronic injections of CS were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with vehicle. IOP was daily or weekly assessed by a tonometer. Retinal function was assessed by scotopic electroretinography (ERG) and the visual pathway by flash visual evoked potentials (VEPs), whereas the retinal and optic nerve head structure were examined by histologic analysis., Results: A single injection of 8 mg (but not 2 or 4 mg) CS induced a significant increase of IOP. The increase of IOP induced by a single injection of 8 mg CS lasted for 7 days, whereas chronic (weekly) administration during 10 weeks induced a significant and sustained increase in IOP compared with eyes injected with vehicle. A significant decrease of scotopic ERG a- and b- wave amplitude was observed after 6 and 10 weeks of CS administration. Moreover, a significant decrease in scotopic flash VEP N2-P2 component amplitude was observed in eyes treated with CS for 6 and 10 weeks. A significant loss of ganglion cell layer cells and optic nerve axons was observed in eyes receiving CS for 10 weeks., Conclusions: These results suggest that exogenous CS simulates the accumulation of CS in primary open-angle glaucoma and that increased amounts of CS could play a key role in the IOP dysregulation characteristic of glaucoma.

Objective: To evaluate the rhythm of intraocular pressure (IOP) in healthy domestic cats with no evidence of ocular disease and to analyze the influence of photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of cat IOP., Animals: All animals were Domestic Short-haired cats; 30 were without systemic or ocular diseases, classified as follows: 12 male intact adult cats, five intact adult female, five adult spayed female, and eight male cats; the latter were less than 1 year of age. In addition, five adult cats with uveitis and three adult cats with secondary glaucoma were included., Procedure: IOP was assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks. Eight animals from the same group were then kept under constant darkness for 48 h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females, and in eight young cats, as well as in five adult cats with uveitis and three glaucomatous cats., Results: Consistent, daily variations in IOP were observed in animals exposed to a light-dark cycle, with maximal values during the night. In cats exposed to constant darkness, maximal values of IOP were observed at subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal-nocturnal variations) persisted in intact females, spayed females, and young animals, as well as in uveitic and glaucomatous eyes., Conclusions: The present results indicate a daily rhythm of cat IOP, which appears to persist in constant darkness, suggesting some level of endogenous circadian control. In addition, daily variations of cat IOP seem to be independent of gender, age, or ocular diseases (particularly uveitis and glaucoma).

Purpose: To study the effect of acute or chronic intracameral injection of hyaluronic acid on intraocular pressure (IOP) in rats., Methods: Acute or chronic injections of hyaluronic acid were performed unilaterally in the rat eye's anterior chamber, whereas the contralateral eye was injected with saline solution. IOP was assessed daily or weekly by a tonometer in conscious rats. IOP was also assessed in both experimental groups at several intervals during the light-dark cycle., Results: A single injection of hyaluronic acid induced an increase of IOP that lasted for 8 days (P < 0.01), whereas its chronic administration during 9 weeks induced a significant and sustained increase in IOP, compared with the eye injected with vehicle (P < 0.01). This hyaluronic acid-induced hypertension was significantly decreased by the application of 1 drop of brimonidine (0.2%), latanoprost (0.005%), or timolol (0.5%). Significant daily variations of IOP were observed in both control and hyaluronic acid-injected eyes, peaking during the dark phase (P < 0.001, ANOVA)., Conclusions: These results suggest that the intracameral administration of hyaluronic acid could be a model of ocular hypertension in rats.

: Retinal ischemia could provoke blindness. At present, there is no effective treatment against retinal ischemic damage. Strong evidence supports that glutamate is implicated in retinal ischemic damage. We investigated whether a brief period of global or ocular hypothermia applied 24 h before ischemia (i.e. hypothermic preconditioning, HPC) protects the retina from ischemia/reperfusion damage, and the involvement of glutamate in the retinal protection induced by HPC. For this purpose, ischemia was induced by increasing intraocular pressure to 120 mm Hg for 40 min. One day before ischemia, animals were submitted to global or ocular hypothermia (33°C and 32°C for 20 min, respectively) and fourteen days after ischemia, animals were subjected to electroretinography and histological analysis. Global or ocular HPC afforded significant functional (electroretinographic) protection in eyes exposed to ischemia/reperfusion injury. A marked alteration of the retinal structure and a decrease in retinal ganglion cell number were observed in ischemic retinas, whereas global or ocular HPC significantly preserved retinal structure and ganglion cell count. Three days after ischemia, a significant decrease in retinal glutamate uptake and glutamine synthetase activity was observed, whereas ocular HPC prevented the effect of ischemia on these parameters. The intravitreal injection of supraphysiological levels of glutamate induced alterations in retinal function and histology which were significantly prevented by ocular HPC. These results support that global or ocular HPC significantly protected retinal function and histology from ischemia/reperfusion injury, probably through a glutamate-dependent mechanism. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to elucidate whether post-ischemic enriched environment (EE) housing protects the retina from ischemic damage in adult rats, and the involvement of glutamate in retinal protection induced by EE housing. For this purpose, ischemia was induced by increasing intraocular pressure to 120mmHg for 40min. After ischemia, animals were housed in a standard environment (SE) or EE and subjected to electroretinography and histological analysis. EE housing afforded significant functional protection in eyes exposed to ischemia/reperfusion injury. A marked reduction in retinal thickness and ganglion cell number, and an increase in Müller cell glial fibrillary acidic protein (GFAP) levels were observed in ischemic retinas from SE-housed animals, which were reversed by EE housing. A deficit in anterograde transport from the retina to the superior colliculus was observed in SE- but not in EE-housed animals. In SE-housed animals, ischemia induced a significant decrease in retinal glutamate uptake and glutamine synthetase activity, whereas EE housing reversed the effect of ischemia on these parameters. The intravitreal injection of supraphysiological levels of glutamate partially reproduced retinal alterations induced by ischemia/reperfusion, which were abrogated by EE housing. These results indicate that EE housing significantly protected retinal function and histology from ischemia/reperfusion injury in adult rats, likely through a glutamate-dependent mechanism. [Copyright &y& Elsevier]

Abstract: An experimental model of pressure-induced optic nerve damage would greatly facilitate the understanding of the cellular events leading to ganglion cell death, and how they are influenced by intraocular pressure and other risk factors associated to glaucoma. The aim of the present report was to study the effect of a long-term increase of intraocular pressure in rats induced by intracameral injections of hyaluronic acid with respect to electroretinographic activity and retinal and optic nerve histology. For this purpose, hyaluronic acid was injected weekly in the rat anterior chamber of one eye, whereas the contralateral eye was injected with saline solution. The results showed a significant decrease of oscillatory potentials and a- and b-wave amplitude of the scotopic electroretinogram after 3 or 6 weeks of hyaluronic acid administration, respectively. These parameters were further reduced after 10 weeks of treatment with hyaluronic acid. No significant changes in anterior chamber angle structures from hyaluronic acid- and vehicle-injected eyes were observed, whereas a significant loss of ganglion cell layer cells and of optic nerve axons were detected in animals that received hyaluronic acid for 10 weeks, as compared to eyes injected with saline solution. In summary, present results indicate that the chronic administration of hyaluronic acid induced a significant decrease in the electroretinographic activity and histological changes in the retina and optic nerve that seem consistent with some features of chronic open-angle glaucoma. Therefore, this could be an experimental model to study the cellular mechanisms by which elevated intraocular pressure damages the optic nerve and the retina. [Copyright &y& Elsevier]