Mechanisms of age-related macular degeneration

Dark adaptation and the retinoid cycle of vision.

RPE lipofuscin and its role in retinal pathobiology.

Taurine is an organic osmolyte involved in cell volume regulation, and provides a substrate for the formation of bile salts. It plays a role in the modulation of intracellular free calcium concentration, and although it is one of the few amino acids not incorporated into proteins, taurine is one of the most abundant amino acids in the brain, retina, muscle tissue, and organs throughout the body. Taurine serves a wide variety of functions in the central nervous system, from development to cytoprotection, and taurine deficiency is associated with cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage to retinal neurons. All ocular tissues contain taurine, and quantitative analysis of ocular tissue extracts of the rat eye revealed that taurine was the most abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary body. In the retina, taurine is critical for photoreceptor development and acts as a cytoprotectant against stress-related neuronal damage and other pathological conditions. Despite its many functional properties, however, the cellular and biochemical mechanisms mediating the actions of taurine are not fully known. Nevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body. Interestingly, taurine satisfies many of the criteria considered essential for inclusion in the inventory of neurotransmitters, but evidence of a taurine-specific receptor has yet to be identified in the vertebrate nervous system. In this report, we present a broad overview of the functional properties of taurine, some of the consequences of taurine deficiency, and the results of studies in animal models suggesting that taurine may play a therapeutic role in the management of epilepsy and diabetes.

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Review : Taurine : a “very essential” amino acid

A degeneration of the retinal photoreceptor cells develops in cats when casein is the source of dietary protein Amino acid profiles indicate that the degeneration is associated with a selective decrease in plasma and retinal taurine concentrations A sulfur amino acid deficit in the casein diet combined with specific amino acid requirements of the cat appear related to this unique expression of taurine deficiency

https://science.sciencemag.org/content/sci/188/4191/949.full.pdf

Retinal degeneration associated with taurine deficiency in the cat.

Mutations in the gene encoding ABCR are responsible for Stargardt macular dystrophy. Here we show by immunofluorescence microscopy and western-blot analysis that ABCR is present in foveal and peripheral cone, as well as rod, photoreceptors. Our results suggest that the loss in central vision experienced by Stargardt patients arises directly from ABCR-mediated foveal cone degeneration.

ABCR expression in foveal cone photoreceptors and its role in Stargardt macular dystrophy.

All cats fed a taurine-free casein diet for 23 weeks have shown a nondetectable electroretinogram (ERG) in association with a plasma and retinal taurine deficiency. In the present study, the casein diet was supplemented with either taurine or taurine precursors (methionine or cysteine) for 23 weeks to see if retinal function would be preserved. Cats fed the casein diet supplemented with methionine or cysteine showed ERG's reduced in amplitude and delayed in implicit time and had plasma and retinal taurine levels that were well below normal by 23 weeks. Only those cats given taurine in the diet (i.e., those fed chow or casein supplemented with taurine) retained normal ERG function and normal plasma and retinal taurine concentrations. These findings establish a role for taurine in maintaining normal retinal function in the cat.

Retinal degeneration in cats fed casein. II. Supplementation with methionine, cysteine, or taurine.

Kittens and adult cats fed a semipurified diet containing casein developed a retinal degeneration that initially involved photoreceptor outer segments in the area centralis. By electron microscopy, cone and rod outer segment lamellar discs could be seen to become vesiculated, frayed, disoriented and twisted. Shortening and subsequent disappearance of outer segments was followed by loss of photoreceptor nuclei, primarily in the area centralis but also in the midperipheral retina. The electroretinogram (ERG) indicated progressive reduction in cone and rod amplitudes and a delay in the temporal aspects of the cone response. When dietary casein was replaced by egg albumin in the diets of cats with minimal to moderately advanced degeneration, the degeneration was reversed; rod ERG function and structure returned essentially to normal, whereas some abnormalities of cone outer segment structure and a delay in the temporal aspects of the cone ERG persisted. The data provide strong evidence that dietary casein is a factor in this retinopathy and suggest that an alteration in protein metabolism of the photoreceptor may result from the dietary protein inadequacy.

An ultrastructural study of nutritionally induced and reversed retinal degeneration in cats.

Plasma free amino-acids were measured in 41 patients with hereditary chorio-retinal degenerations including 26 with retinitis pigmentosa and five with gyrate atrophy of the choroid, six relatives of patients with gyrate atrophy, and 13 normal subjects. Patients with gyrate atrophy had very increased levels of ornithine and slightly decreased mean lysine values. Most relatives had slightly increased ornithine. Taurine, known to be deficient in the plasma of casein-fed cats with photoreceptor degeneration, was normal in all patients. Amino-acid precursors and metabolites of ornithine and taurine were also normal in the plasma. Although the association of high ornithine and gyrate atrophy appears constant, high levels of ornithine alone do not necessarily lead to this degeneration; one patient with known hyperammonaemia, homocitrullinuria and a tenfold increase in plasma ornithine was found to have a normal fundus appearance and normal electroretinogram.

https://bjo.bmj.com/content/bjophthalmol/60/2/142.full.pdf

Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine.

A full-field system is described for recording the human electroretinogram (ERG). The full-field stimulus and background minimize the problem of stimulation of large areas of the retina by stray light. Normal responses are illustrated under stabilized conditions of adaptation to single flashes of white light, as well as short wavelength and long wavelength light stimuli matched in brightness for the cone and rod systems, respectively. In this system, measurement of the temporal aspects of the ERG not only helps to establish diagnoses, but also provides information about visual prognosis in patients with hereditary retinal disease.

Arnold R. Rabin

Papers

ABCR expression in foveal cone photoreceptors and its role in Stargardt macular dystrophy.

Retinal degeneration in cats fed casein. II. Supplementation with methionine, cysteine, or taurine.

An ultrastructural study of nutritionally induced and reversed retinal degeneration in cats.

Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine.

A full-field system for clinical electroretinography.