Interphotoreceptor retinoid-binding protein (IRBP) in progressive rod-cone degeneration (prcd)--biochemical, immunocytochemical and immunologic studies.
Interphotoreceptor retinoid-binding protein (IRBP) is synthesized and secreted by photoreceptor cells and is thought to facilitate the transport of retinoids during the visual cycle as well as fatty acids essential to the maintenance of normal outer segment membranes. Proteins such as IRBP, which are unique to the photoreceptor cells in the retina, are prime candidates in the consideration of biochemical defects which could contribute to photoreceptor cell degeneration in man and animals. In this study, the association between IRBP and retinal degeneration was examined using the progressive rod-cone degeneration (prcd) mutant retina in dogs as an animal model. This study shows that loss of IRBP is not an early occurrence in prcd. IRBP is present in relatively normal amounts and distribution even at 1.7 years of age, a time when there is extensive visual cell disease and degeneration. By 2.7-3.0 years of age, IRBP loss correlates with the severity of the disease and concomitant loss of photoreceptor cells. IRBP immunoreactivity was present in the interphotoreceptor matrix (IPM) as long as inner segments were present to a significant degree. The late loss of IRBP immunoreactivity seems to be, therefore, the result of advanced degeneration and end-stage atrophy of the retina. In addition, immunological studies were carried out in order to examine the possible role of an autoimmune response against IRBP in the disease cascade. Normal, heterozygote and prcd-affected dogs had measurable antibody titers to IRBP, but there was no correlation between disease state and antibody levels.
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892.
B
B
Wiggert
G
G
Kutty
K O
KO
Long
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L
Inouye
I
I
Gery
G J
GJ
Chader
G D
GD
Aguirre
D000367:Age Factors; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D015152:Blotting, Northern; D015153:Blotting, Western; D004285:Dogs; D005136:Eye Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D010786:Photoreceptor Cells / Q000473:pathology; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D000099214:Retinol-Binding Proteins, Interstitial
D001323:Autoantibodies; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial