Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have studied degeneration in the rd10 mice both by immunocytochemistry and TUNEL-labeling of retinal cells, and through electrophysiological recordings. The cell degeneration in the retina of rd10 mice produced appreciable morphological changes in rod and cone cells by P20. Retinal cell death is clearly observed in the central retina and it peaked at P25 when there were 800 TUNEL-positive cells per mm(2). In the central retina, only one row of photoreceptors remained in the outer nuclear layer by P40 and there was a remarkable deterioration of bipolar cell dendrites postsynaptic to photoreceptors. The axon terminals of bipolar cells also underwent atrophy and the inner retina was subject to further changes, including a reduction and disorganization of AII amacrine cell population. Glutamate sensitivity was tested in rod bipolar cells with the single cell patch-clamp technique in slice preparations, although at P60 no significant differences were observed with age-matched controls. Thus, we conclude that rod and cone degeneration in the rd10 mouse model is followed by deterioration of their postsynaptic cells and the cells in the inner retina. However, the functional preservation of receptors for photoreceptor transmission in bipolar cells may open new therapeutic possibilities.

Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5 flox/flox mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases. Retinal ganglion cells (RGCs) are the only projecting neurons of the retina. Their axons form the optic nerve and transmit visual information to the brain. RGCs undergo apoptotic cell death in a stereotyped manner during development and in response to injury, in glaucoma and other optic neuropathies. 1 Degeneration of RGCs is often modeled by optic nerve transection (ONT), which leads to the death of these central nervous system neurons. 2 The mechanisms of RGC death are still a matter of intense investigation, and several factors including growth factor deprivation and oxidative stress have been proposed to participate in RGC degeneration in glaucoma and after ONT. 1,3 Autophagy is an intracellular catabolic pathway, which degrades cell components, toxic aggregates and damaged organelles and recycles them as basic building blocks in order to maintain cellular homeostasis. 4 Autophagy begins with the formation of a double membrane, sequestering parts of the cytosol and finally closing to form an autophagosome. This autophagosome subsequently fuses with lysosomes, thus, enabling degradation of the engulfed material. 4 Autophagy represents a cytoprotective response in many cell types 5 and its deregulation is implicated in many pathological conditions, including cancer, infectious diseases and neurodegeneration. 6 The role of autophagy in neuronal physiology is still far from being completely understood. 7,8 On one hand, autophagy is essential in preventing spontaneous neurodegeneration in mice, as deletion of the autophagy regulators Atg5, Atg7 and FIP200 in neuronal precursors induces cell death, accumulation of damaged ubiquitinated proteins and premature lethality. 9-11 Similarly, upregulation of autophagy decreases the accumulation of protein aggregates in several neurodegenerative proteinopathies. 12,13 Conversely autophagy triggers neuronal death under seve...

ABSTRACT.Purpose: Diabetes mellitus (DM) affects corneal biomechanical parameters. We compared analyses using ORA (Ocular response analyser) and Corvis ST to determine the influence of disease duration, hyperglycaemia and haemoglobin A1c (HbA1c) levels on these parameters. Methods: This observational, cross-sectional, observer-masked study assessed one eye of 94 consecutive DM patients and 41 healthy subjects. Two DM groups were analysed: the uncontrolled DM group (n = 54) (HbA1c ≥ 7%) and the controlled DM group (n = 40) (HbA1c < 7%). Central corneal thickness (CCT) was measured by ultrasonic pachymetry and intraocular pressure (IOP) by Goldmann applanation tonometry. ORA and Corvis ST analyses were performed to evaluate the changes. Results: Most of the Corvis ST parameters [Deformation amplitude (DA), A1 and A2 times, A1 velocity] in the uncontrolled DM group eyes were found to be significantly different to controls and controlled DM group eyes (p = 0.005, p = 0.001, p < 0.0001, p = 0.002, respectively). DA on the Corvis ST was correlated with blood glucose concentration (p = 0.004) and HbA1c percentage (p = 0.002). ORA corneal hysteresis was significantly lower in diabetic patients with elevated HbA1c than in control subjects (p = 0.001) and was affected by disease duration (p = 0.037), whereas the corneal resistance factor remained unaltered. Conclusions: A poor glucose control in DM affects corneal biomechanics measured by ORA and Corvis ST, which may cause high IOP measurements independent of CCT. The measurement of the corneal biomechanics should be taken into consideration in the clinical practice.

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400–500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated.

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.