Purchase this article with an account.
Cheryl Mae Craft, Joseph S Pak, Janise D Deming, Lawrence L Rife, Bruce M Brown; Protecting Cone Photoreceptor Structure & Function: Age-Related Cone Degeneration Involves Cone Arrestin (Arr4) Expression. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3030.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Visual arrestins (Arr) play an essential role in GPCR shutoff of S- and M-opsins. When electrophysiological responses are measured for a single cone, Arr1 can substitute for Arr4 in cone pigment desensitization (Nikonov et al., Neuron 2008:59,462). Additional studies reveal that each Arr contributes its own, unique roles to modulate other cellular functions. When Arr1 is defective in mouse, retinal degeneration occurs, modulation of N-ethylmaleimide sensitive factor ATPase activity & light adaptation are both compromised (Huang et al., JNS 2010: 30, 9381; Brown et al., IOVS 2010: 51, 2372). Deficits in Arr4 lead to impaired ERGs, visual acuity & contrast sensitivity (Craft et al., submitted). Are cone structure & photopic functions compromised with increasing age when Arr4 is not expressed?
Using a combination of photopic ERG measurements, quantitative immunohistochemistry of retinal sections, and immunoblot analysis of retinal homogenates, we investigated the retinal phenotypes of Arr4-/- on a control (WT) or Neural retina leucine zipper transcription factor null background (Nrl-/- provided by A. Swaroop) in younger (1.5-3 mo) & older (7+ mo) mice (12:12 light/dark).
Younger Arr4-/- mice had similar a- and b-wave implicit times, but higher b-wave flash amplitudes and flicker amplitudes when compared to controls, especially in Arr4-/-Nrl-/-. In contrast, in older Arr4-/- mice, all amplitudes and flicker responses were reduced in magnitude compared to controls. Although the cone photoreceptor numbers were similar between groups at 1.5 mo, ventral M-opsin immunoreactive staining intensity was elevated in the Arr4-/-. Expression levels revealed an increase in M-opsin & a decrease in S-opsin immunoreactive expression in 1.5 mo Arr4-/-Nrl-/- retina. In contrast, in older Arr4-/- mice, M-opsin cones were significantly decreased, expression levels were diminished, & Arr4-/-Nrl-/- mice had reduced & mislocalized cone opsins.
Our study reveals that cone photoreceptor structure & functions are compromised and cones degenerate with age without cone Arr4 expression. Arr4-/- mice display distinct phenotypic differences when compared to their age-matched controls, which suggests that Arr4 protects cones & modulates essential functions in vision that are not fulfilled by the co-expression of Arr1, despite its high expression levels in all mouse cones.
This PDF is available to Subscribers Only