Molecular biological, histological and flicker electroretinographic results have established that mice have two cone photopigments, one peaking near 350 nm (UV-cone pigment) and a second near 510 nm [midwave (M)-cone pigment]. The goal of this investigation was to measure the action spectra and absolute sensitivities of the UV-cone-and M-cone-driven b-wave responses of C57BL/6 mice. To achieve this goal, we suppressed rod-driven signals with steady or flashed backgrounds and obtained intensity-response relations for conedriven b-waves elicited by narrowband flashes between 340 and 600 nm. The derived cone action spectra can be described as retinal 1 pigments with peaks at 355 and 508 nm. The UV peak had an absolute sensitivity of ϳ8 nV/(photon m 2 ) at the cornea, approximately fourfold higher than the M peak. In an attempt to isolate UV-cone-driven responses, it was discovered that an orange conditioning flash ( Ͼ 530 nm) completely suppressed ERG signals driven by both M pigment-and UV pigment-containing cones. Analysis showed that the orange flash could not have produced a detectable response in the UV-cone pathway were their no linkage between M pigmentand UV pigment-generated signals. Because cones containing predominantly the UV and M pigments have been shown to be located largely in separate parts of the mouse retina (Szel et al., 1992), the most probable linkage is coexpression of M pigment in cones primarily expressing UV pigment. New histological evidence supports this interpretation (Gloesman and Ahnelt, 1998). Our data are consistent with an upper bound of ϳ3% coexpression of M pigment in the cones that express mostly the UV pigment.

This is a brief review of data obtained by analyzing the morphology and the physiology of the retinas in rd/rd and normal, wt mice, aged 10-90 days. Second-order neurons of the rd/rd show abnormalities that start with the anomalous development of rod bipolar cells around P10 and culminate with the atrophy of dendrites in cone bipolar cells, mostly evident at P90. Horizontal cells remodel considerably. Cone-mediated ERGs, (recorded between 13 and 16 days of age) have reduced a-wave and b-wave amplitudes and longer b-wave latency and duration. B-wave abnormalities indicate specific postreceptoral dysfunction. Morphological and ERG changes in rd/rd retinas are consistent with substantial inner retinal remodeling associated to photoreceptor degeneration.

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Guanylate Cyclase-Activating Protein 1 (GCAP1) regulates the enzymatic activity of the photoreceptor guanylate cyclases (GC), leading to inhibition or activation of the cyclic guanosine monophosphate (cGMP) synthesis depending on its Ca2+- or Mg2+-loaded state. By genetically screening a family of patients diagnosed with cone-rod dystrophy, we identified a novel missense mutation with autosomal dominant inheritance pattern (c.332A>T; p.(Glu111Val); E111V from now on) in the GUCA1A gene coding for GCAP1. We performed a thorough biochemical and biophysical investigation of wild type (WT) and E111V human GCAP1 by heterologous expression and purification of the recombinant proteins. The E111V substitution disrupts the coordination of the Ca2+ ion in the high-affinity site (EF-hand 3, EF3), thus significantly decreasing the ability of GCAP1 to sense Ca2+ (∼80-fold higher Kdapp compared to WT). Both WT and E111V GCAP1 form dimers independently on the presence of cations, but the E111V Mg2+-bound form is prone to severe aggregation over time. Molecular dynamics simulations suggest a significantly increased flexibility of both the EF3 and EF4 cation binding loops for the Ca2+-bound form of E111V GCAP1, in line with the decreased affinity for Ca2+. In contrast, a more rigid backbone conformation is observed in the Mg2+-bound state compared to the WT, which results in higher thermal stability. Functional assays confirm that E111V GCAP1 interacts with the target GC with a similar apparent affinity (EC50); however, the mutant shifts the GC inhibition out of the physiological [Ca2+] (IC50E111V ∼10 μM), thereby leading to the aberrant constitutive synthesis of cGMP under conditions of dark-adapted photoreceptors.

Background Systemic vascular involvement in COVID-19 has been identified in several patients: not only endothelial derangement and increased permeability are reported to be early hallmarks of organ damage in patients with COVID-19 but are also the most important cause of worsening of clinical conditions in severe cases of SARS-CoV-2 infection. There are several reasons to hypothesize that the eye, and the retina in particular, could be a target of organ damage in SARS-CoV-2 infection. Methods This cohort observational study analyzes OCT angiography and structural OCT of 70 post-COVID-19 patients evaluated at 1-month hospital discharge and 22 healthy control subjects. Primary outcomes were macular vessel density (VD) and vessel perfusion (VP); structural OCT features were evaluated as secondary outcomes. In addition, patients and healthy volunteers were evaluated for best corrected visual acuity, slit lamp photograph, and fundus photo image. Results VD and VP in 3 × 3 and 6 × 6 mm scans for SCP and DCP showed no significant differences between the groups. Similarly, CMT and GCL did not reveal significant differences between post-COVID-19 and healthy patients. Nine patients (12.9%) featured retinal cotton wool spots and 10 patients had vitreous fibrillary degeneration. The prevalence of epiretinal membrane and macular hole was similar in the two groups. One case of extra papillary focal retinal hemorrhage was reported in the post-COVID-19 group. Conclusions Macula and perimacular vessel density and perfusion resulted unaltered in mild post-COVID-19 patients at 1-month hospital discharge, suggesting no or minimal retinal vascular involvement by SARS-CoV-2.

Age-related macular degeneration (AMD) is a retinal neurodegenerative disease whose development and progression are the results of a complex interaction between genetic and environmental risk factors. Both oxidative stress and chronic inflammation play a significant role in the pathogenesis of AMD. Experimental studies in rats with light-induced photoreceptors degeneration demonstrated that saffron may protect photoreceptor from retinal stress, preserving both morphology and function and probably acting as a regulator of programmed cell death, in addition to its antioxidant and anti-inflammatory properties. Recently, a randomized clinical trial showed that in patients with early AMD, dietary supplementation with saffron was able to improve significantly the retinal flicker sensitivity suggesting neuroprotective effect of the compound. Here, we examine the progress of saffron dietary supplementation both in animal model and AMD patients, and discuss the potential and safety for using dietary saffron to treat retinal degeneration.

The early morphologic involvement of the GCL+IPL and INL+OPL layers in ARM eyes, as revealed by the ASA, could be related to early anatomic changes described in the inner retina of ARM eyes. This finding may represent a morphologic correlation to the deficits in postreceptoral retinal function in ARM eyes.

Steady-state pattern electroretinogram (PERG) in response to sinusoidal gratings (1.7 c/deg spatial frequency; 9 x 9 deg field size) temporally modulated (sinusoidally) at 8 Hz were recorded in 40 insulin-dependent diabetics and 28 age-matched normal subjects. Visual acuity was greater than or equal to 20/20 in all 40 patients; 31 (62 eyes) showed no sign of retinopathy and nine (18 eyes) showed a few microaneurysms on fluorescein angiography. Insulin-dependent diabetics showed a significant reduction in the PERG mean amplitude as compared with age-matched control subjects (one-way analysis of variance: p less than 0.0001). Significant differences were observed between normals and diabetics without retinopathy (Scheffé test: p less than 0.0001), normals and diabetics with early retinopathy (Scheffé test: p less than 0.0001), no retinopathy and early retinopathy patients (Scheffé test: p less than 0.05). In diabetics without retinopathy multifactorial analysis of variance revealed a significant effect of age of onset of the disease (p less than 0.01) and an interaction effect between age of onset and duration (p less than 0.001) on PERG amplitude. These results suggest a possible use of the steady-state PERG to detect early macular dysfunction in insulin-dependent diabetics.