The difference between the medians was not statistically significant (P = 0

The difference between the medians was not statistically significant (P = 0.489). RGCs exhibited response saturation, only 14% of P23H rat RGCs showed response saturation. TPMPA decreased the responses of saturating SD rat RGCs to low (6% to 13%) grating contrasts but increased the response to the highest contrast (83%) tested. JNJ16259685 did not significantly affect the contrast response functions of either saturating or non-saturating SD rat RGCs. In contrast, both TPMPA and JNJ16259685 increased the responses of saturating and non-saturating P23H rat RGCs to all grating contrasts. Neither TPMPA nor JNJ16259685 affected the contrast thresholds of SD rat RGCs, but both antagonists lowered the contrast thresholds of P23H rat RGCs. Overall, the findings show that GABACR and mGluR1 antagonists have differential effects on the contrast response functions of SD and P23H rat RGCs. Notably, these receptor antagonists increase the responsiveness of P23H rat RGCs to both low and high contrast visual stimuli. Introduction Contrast is an important parameter in assessing visual function. A person with reduced contrast sensitivity will have difficulty with many common daily tasks, such as detecting curbs or stairs, reading facial expressions, and driving at night. In clinical practice, contrast sensitivity charts are widely used to test the ability of a patient to perceive small differences in luminance between adjacent surfaces. In patients with retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, contrast sensitivity may be diminished while visual acuity is still good as determined with a standard eye chart [1C5]. The neural mechanisms underlying the contrast sensitivity reduction are currently unknown. In both retinitis pigmentosa and age-related macular Tenofovir (Viread) degeneration, there is MDS1-EVI1 a loss of photoreceptors with concomitant remodeling of cells within the inner retina (for review see 6, 7). Details of the changes that emerge within the inner retina following degeneration of photoreceptors have come primarily from studies conducted in animal models of retinitis pigmentosa. Horizontal cells and bipolar cells, which are postsynaptic to photoreceptors, appear to be affected initially. Horizontal cells retract their dendrites [8, 9] and may grow processes directed towards in inner plexiform layer [10, 11]. Bipolar cells also retract their dendrites [8, 9], and in ON bipolar cells there is a down-regulation of dendritic mGluR6 receptors and TRPM1 channels [9, 11, 12]. Amacrine cells, which are postsynaptic to bipolar cells, are likewise affected. Morphological alterations in one type of amacrine cellCthe AII amacrine cellChave been described in several animal models of retinitis pigmentosa [9, 13, 14]. In addition, these amacrine cells show elevated phosphorylation of the gap junction subunit Cx36 [15], which may increase electrical coupling between AII Tenofovir (Viread) amacrine cells. In the inner retinas of degenerate retinas, alterations in the expression of AMPA, glycine, GABAA, GABAC and NMDA receptors have been described [16, 17]. Increased levels of synaptic proteins in both bipolar cells and amacrine cells in the degenerate retina have also been reported [18], suggesting increased synaptic activity in these cells. These and very likely other, yet to be discovered, changes that take place in inner retinal neurons Tenofovir (Viread) may contribute to the loss of contrast sensitivity in the patients with retinitis pigmentosa and age-related macular degeneration. Previously, I showed that the GABACR antagonist TPMPA and the mGluR1 antagonist JNJ16259685 increase the sensitivity of retinal ganglion cells (RGCs) in the P23H rat model of retinitis pigmentosa to brief flashes. Tenofovir (Viread)