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Effects of Low AIPL1 Expression on Phototransduction in Rods

¹From the Howe Laboratory and ³Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts; ²Hafter Research Laboratories, Pennsylvania College of Optometry, Elkins Park, Pennsylvania; the ⁴Departments of Cell Biology and ⁵Ophthalmology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma; and the ⁶Department of Physiological Science and ⁷Jules Stein Institute, University of California at Los Angeles, Los Angeles, California.

PURPOSE. To investigate the impact of aryl hydrocarbon receptor-interacting protein-like (AIPL)-1 on photoreception in rods.

METHODS. Photoresponses of mouse rods expressing lowered amounts of AIPL1 were studied by single-cell and electroretinogram (ERG) recordings. Phototransduction protein levels and enzymatic activities were determined in biochemical assays. Ca²⁺ dynamics were probed with a fluorescent dye. Comparisons were made to rods expressing mutant Y99C guanylate cyclase activating protein (GCAP)-1, to understand which effects arose from elevated dark levels of cGMP and Ca²⁺.

RESULTS. Except for PDE, transduction protein levels were normal in low-AIPL1 retinas, as were guanylate cyclase (GC), rhodopsin kinase (RK), and normalized phosphodiesterase (PDE) activities. Y99C and low-AIPL1 rods were more sensitive to flashes than normal, but flash responses of low-AIPL1 rods showed an abnormal delay, reduced rate of increase, and longer recovery not present in Y99C rod responses. In addition, low-AIPL1 rods but not Y99C rods failed to reach the normal light-induced minimum in Ca²⁺ concentration.

CONCLUSIONS. Reduced AIPL1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in Ca²⁺. Not all changes were attributable to decreased PDE or to elevated cGMP and Ca²⁺ in darkness. Therefore, AIPL1 directly or indirectly affects more than one component of phototransduction.

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