Rod-derived cone viability factor (RdCVF) is a thioredoxin-like protein, which has therapeutic potential for rod-cone dystrophies such as retinitis pigmentosa (RP). Cone loss in rodent models of RP is effectively reduced by RdCVF treatment. In this study, we investigate the physiological role of RdCVF in the retina by analyzing the phenotype of the mouse lacking the RdCVF gene, Nxnl1. Although the mice do not show an obvious developmental defect, an age-related reduction of both cone and rod function and a delay in the dark-adaptation of the retina are recorded by electroretinogram (ERG). This functional change is accompanied by a 17% reduction in cone density and a 20% reduction in thickness of the outer nuclear layer. The transcriptome of the retina reveals early changes in the expression of genes involved in programmed cell death, stress-response and redox-signaling, which is followed by a generalized injury response with increased microglial activation, GFAP, FGF2 and lipid peroxidation levels. Furthermore, cones of the mice lacking Nxnl1 are more sensitive to oxidative stress with a reduction of 65% in the cone flicker ERG amplitude measured under hyperoxic conditions. We show here that the RdCVF gene, in addition to therapeutic properties, has an essential role in photoreceptor maintenance and resistance to retinal oxidative stress.

In the literature taurine is characterized as a non-specific growth or blood clotting factor, an antioxidant, a membrane protector, or a regulator of calcium ion homeostasis, just as vitamins A, D, E, F, and K are similarly characterized. On the basis of recent finding concerning the relationship between taurine and the aldehyde of vitamin A-retinal (Petrosian and Haroutounian, 1988, 1998; Petrosian et al., 1996), as well as on the basis of data from the literature, we now suggest a hypothesis that taurine promotes the bioavailability of the lipid soluble vitamins A, D, E, K, and F, probably by forming different types of water soluble, easily hydrolyzable complexes. It is quite possible that the ability of taurine to convert lipids and lipid soluble substances into a water soluble state is the key to understanding the unusually wide diversity of biological phenomena associated with taurine. This form of delivery may be an additional, secondary mechanism for the transport of lipid soluble vitamins, which was probably acquired early in evolution, and remains extremely important for mammals and humans directly after birth for a variety of physiological functions such as: vision in normal and in emergency situations, rapid blood clotting, sperm eruption, and situations requiring a prompt consumption of lipid soluble vitamins characteristic of excitable systems. Clearly, the role of taurine in the physiology of the water insoluble vitamins remains an enigma and is worthy of further investigations.

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