Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina.

BACKGROUND:The rod photoreceptor cGMP-gated cation channel, consisting of three α- and one β subunit, controls ion flow into the rod outer segment In addition to the β-subunit, the Cngb1 locus encodes an abundant soluble protein, that binds stoichiometrically to rod photoreceptor cGMP phosphodiesterase type 6 (PDE6). To examine the in vivo functional role of Gduanyu372 we generated opsin promoter-driven transgenic mice overexpressing Gduanyu372 three-fold specifically in rod photoreceptors. RESULTS:In the Gduanyu372 overexpressing transgenic mice (tg), the endogenous channel β-subunit, cGMP phosphodiesterase α-subunit, peripherin2/RDS and guanylate cyclase I were present at WT levels and were properly localized within the While localized properly within two proteins cGMP phosphodiesterase α-subunit (1.4-fold) and cGMP-gated cation channel α-subunit (1.2-fold) were moderately, but significantly elevated. Normal stratification of all retinal layers was observed, and were stable in numbers but were 19% shorter than WT. Analysis of the photoresponse using electroretinography (ERG) showed that tg mice exhibit no change in sensitivity indicating overall normal rod function, however two parameters of the photoresponse significantly differed from WT responses. Fitting of the rising phase of the ERG a-wave to an accepted model of phototransduction showed a two-fold increase in phototransduction gain in the tg mice. The increase in gain was confirmed in isolated retinal tissue and by suction electrode recordings of individual rod photoreceptor cells. A measure of response recovery, the dominant time constant (τD) was elevated 69% in isolated retina compared to WT, indicating slower shutoff of the may participate in regulating visual signal transduction through a previously unappreciated role in regulating phototransduction gain and recovery.

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