Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the rat

Abstract

The influence of eye pigmentation and light deprivation on inherited retinal dystrophy has been studied in Royal College of Surgeons (RCS) rats which are pink-eyed and in two congenic strains, RCS- p/+, which are black-eyed and RCS- c, which are albinos. The congenic animals are genetically similar to inbred RCS rats, differing only in pigmentation genes and other genes closely linked to the pigmentation loci. Progression of the disease has been analyzed in a series of animals cytologically with 1–2 μm plastic sections and biochemically by measurement of whole eye extractions of rhodopsin. When the rats are reared in cyclic light (12 hr light-12 hr dark; cage illumination less than 15 ft-c), the rate of photoreceptor degeneration in black-eyed rats is slowed from the rate in pink-eyed rats by about 10 days in the posterior retina. In the far peripheral retina, the disease is slowed by about 30–35 days in the superior half of the eye, along and above the horizontal meridian. No slowing occurs in the inferior half of the eye along the vertical meridian. When pink-eyed RCS and black-eyed RCS- p/+ rats are dark-reared, the pattern of degeneration in both is the same as in black-eyed rats reared in cyclic light. The rhodopsin content of eyes from black-eyed RCS- p/+ rats reared in cyclic light also is the same as that in pink-eyed rats reared in darkness. No difference was found between pink-eyed RCS and albino RCS- c retinas in the rate of the disease or in rhodopsin content. These findings indicate that (1) intrinsic differences exist in different regions of the retina in the rate of retinal dystrophy, (2) black eye pigment slows the progression of the disease as much as does dark-rearing in pink-eyed rats, (3) the very small amount of eye pigment in pink-eyed RCS rats is ineffectual in slowing the rate of the disease from that in albino RCS- c rats, and (4) dark-rearing does not slow the rate of the disease further in black-eyed rats. Additional features of retinal dystrophy in the RCS rat were observed. Some photoreceptor cells survive in clusters immediately adjacent to the optic nerve head and the ora serrata as late as day 96, long after most photoreceptors have disappeared. The rod outer segment debris (extra lamellar material), which is a characteristic of retinal dystrophy in the rat, shows a loss of basophilia and osmiophilia (“blanching”) beginning at days 32–35 in the apical region of the debris in the posterior retina. The debris becomes progressively more “blanched” until about day 96, when most of the debris has lost its basophilia in all regions of the eye; the “blanching” of the membranes correlates closely with the loss of rhodopsin from the eye. The issue of the source of the extra lamellar material is re-examined, and data are provided that indicate the material probably is formed entirely from the breakdown of rod outer segments.