Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

Abstract

METHODS. Albino rats received b-alanine in the drinking water to induce taurine depletion. One month later, half of the animals were exposed to white light (3000 lux) continuously for 48 hours and the rest remained in normal environmental conditions. A control group of animals nontreated with b-alanine also was prepared, and half of them were exposed to light using the same protocol. All the animals were processed 2 months after the beginning of the experiment. Retinas were dissected as wholemounts and immunodetected with antibodies against Brn3a, melanopsin, S-opsin, and L-opsin to label different retinal populations: Brn3a þ retinal ganglion cells (RGCs) (image-forming RGCs), m þ RGCs (non-image-forming RGCs), and S-and L/M-cones, respectively. RESULTS. Light exposure did not affect the numbers of Brn3aþ RGCs or m þ RGCs but diminished the numbers of S-and L/M-cones and caused the appearance of rings devoid of cones, mainly in an ''arciform'' area in the superotemporal retina. Taurine depletion caused a diminution of all the studied populations, with m þ RGCs the most affected, followed by Scones. Light exposure under taurine depletion increased photoreceptor degeneration but did not seem to increase Brn3a þ RGCs or m þ RGCs loss. CONCLUSIONS.Our results document that taurine is necessary for cell survival in the rat retina and even more under light-induced photoreceptor degeneration. Thus, taurine supplementation may help to prevent retinal degenerations, especially those that commence with S-cone degeneration or in which light may be an etiologic factor, such as inherited retinal degenerations, AMD, or glaucoma.

Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

“…Residual photoreceptors in the fovea show major disorganization, resembling severe morphologic changes of photoreceptors in taurinedepleted rhesus monkeys (67,68). Tritanopia and a general functional deficit in cone function are compatible with pronounced S-cone photoreceptor loss that has been reported together with L/M cone loss in taurinedepleted albino rats (10). Increased inner retinal thickness in our patients (Fig.…”

“…TAUT transports nutritional taurine into retinal pigment epithelium cells, which supply it to the photoreceptor cells (8). Nutritional taurine deficiency in cats causes massive photoreceptor degeneration (9), particularly upon light exposure (10), and leads to abnormal electroretinography (ERG) in humans, reversible by intravenous taurine supplementation (11,12). SLC6A6 therefore represents a prime candidate for inherited retinal dystrophy in humans.…”

Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration

“…Two-month-old albino Sprague-Dawley female rats (150-180 g body weight) were obtained from the University of Murcia breeding colony (n = 24) and exposed to 3000 lux of cold fluorescent white light continuously for 48 hours following previously described methods. 2,3,13,15 Another group of animals (n = 8) was used as control group. Experimental animals were processed 1, 2, or 3 months after light exposure (ALE).…”

“…29,59 There is also evidence that there is an interaction between microglial and Müller cells that affects trophic factor release by Müller cells 60 and therefore this interplay may also be important to regulate the responses of Müller cells in different scenarios, such as the regenerating zebrafish retina, 61 in animal models of retinal degenerations 62 and also in cocultures of activated microglia and Müller cells. 60 In this study, we have used our previously described model of light-induced retinal degeneration 2,3,13,15 and immunodetection of cones, Müller and microglial cells to investigate the role of the macro-and microglial cells in the rings of photoreceptor degeneration. To our knowledge, this is the first time that the relationship between cone degeneration, and microglial and macroglial cell reactivity has been analyzed in this model.…”

Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration

“…Finally, all the retinas were prepared for cryostat cross sections following previously described methods. 27,40,41…”