title: Cyclic-nucleotide phosphodiesterase: an early defect in inherited retinal degeneration of C3H mice.
abstract: Cyclic nucleotides have been implicated in the differentiation and function of the vertebrate retina. In the normal retina of DBA mice, the specific activity of cyclic-nucleotide phosphodiesterase (PDE), with cyclic-AMP as the substrate (cAMP-PDE), increases eightfold between the 6th and 20th postnatal day. Kinetic analysis of retinae from newborn mice reveals a PDE with a single Michaelis constant (K(m)) value for cyclic-AMP (low K(m)-PDE). After the 6th postnatal day, a second PDE with a high K(m) for cyclic-AMP (high K(m)-PDE) can be demonstrated. The appearance and increasing activity of the high K(m)-PDE coincides with the differentiation and growth of photoreceptor outer segments. Additionally, the high K(m)-PDE is shown by microchemical techniques to be concentrated in the photoreceptor cell layer and the low K(m)-PDE within the inner layers of the normal retina. In C3H mice afflicted with an inherited degeneration of the photoreceptor layer, the postnatal increase in the specific activity of cAMP-PDE is substantially lower than in the normal retina. The postnatal increase in the specific activity of cAMP-PDE in two regions of the brain of C3H mice is the same as in the normal strain. A deficiency in high K(m)-PDE activity in the C3H retina is evident on the 7th postnatal day, when the activity of low K(m)-PDE, photoreceptor morphology, and rhodopsin content of these retina are essentially normal. In the adult C3H retina, the PDE activity with cyclic-GMP and cyclic-UMP as substrates is significantly below that of the normal retina. These data indicate that an alteration in cyclic-AMP metabolism occurs before photoreceptor cell degeneration in the retinae of C3H mice.
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D000242:Cyclic AMP; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008832:Microchemistry; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000254:growth & development; D012160:Retina / Q000032:analysis / Q000201:enzymology; D012162:Retinal Degeneration / Q000201:enzymology* / Q000235:genetics; D012168:Retinal Pigments / Q000032:analysis; D014020:Tissue Extracts / Q000032:analysis
chemical_list: D012168:Retinal Pigments; D014020:Tissue Extracts; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases