The Role of Arrestins in Visual and Disease Processes of the Eye - Progress in Molecular Biology and Translational Science - page 249

enolase1 in the dark, and upon translocating to the outer segments during
light adaptation, releases its suppression of enolase1 activity. The potential
function of this interaction is not clear as photoreceptors use 75% more
energy in the dark than in the light to maintain the ionic polarization while
the CNG sodium channels are open. 97,98 The current hypothesis is that
increasing glycolysis in the light might have more to do with the production
of NADH than with ATP production as there is clearly an increased need for
reducing agents in light-exposed photoreceptors for reduction of all- trans
retinal produced during rhodopsin activation and reduction of oxidation
by-products from photon flux.

7. ARRESTINS IN DISEASE PROCESSES IN THE EYE

Because of the central role of arrestin1 in the phototransduction pro-
cess, defects arising from mutations in the arrestin1 gene are the basis for a
limited number of visual deficits. Perhaps not surprisingly, based on the
coexpression of arrestin1 and arrestin4 in cones and their ability to substitute
for each other, there have not yet been any diseases identified that associate
with defects in arrestin4.

7.1. Oguchi disease
The most common visual defect associated with mutations in the arrestin1
gene is Oguchi disease, a relatively rare form of stationary night
blindness. 99-101 Instead of the normal 30-40 min required for dark adapta-
tion, patients with Oguchi disease typically require more than 2 h (and up to
5-7 h) to adapt to darkness. 102 Optical coherence tomography measure-
ments indicate that at least for some Oguchi patients, there is a shortening
of the outer segments associated with this arrestin1 deficit which correlates
with delayed recovery in multifocal electroretinogrammeasurements. 103,104
This observation is recapitulated in a mouse arrestin1 knockout model that
shows initial shortening of the outer segments prior to a slow retinal degen-
eration. 105 The underlying mechanism for delayed dark adaptation in these
patients is not clearly defined but is likely related to the removal of all acti-
vated rhodopsin and subsequent regeneration with 11- cis retinal. In the pres-
ence of arrestin1, activated rhodopsin (metarhodopsin) is bound and
stabilized in its metarhodopsin II conformation, 78 which is accessible to
the retinol dehydrogenase for reduction of its retinoid chromophore. 25 In
the absence of

arrestin1, activated rhodopsin accumulates in the