Altered rhodopsin regeneration in diabetic mice caused by acid conditions within the rod photoreceptors.

Purpose: The experiments were designed to provide details on the characteristics of rhodopsin regeneration in the rod photoreceptors of diabetic mice and to evaluate their mechanistic basis.

Methods: A genetically-derived diabetic albino mouse was developed. An excised albino mouse eye preparation was used. The preparation allows for direct measurements of rhodopsin concentration and other spectrally distinct intermediates, and maintains the structural integrity of the compartments involved in rhodopsin regeneration. The experiments were conducted at moderate bleaching levels, averaging 13-14%, with mice that exhibited moderate levels of blood glucose concentration.

Results: Rhodopsin regeneration was delayed in both genetically-derived and streptozotocin-injected diabetic mice when compared to non-diabetic mice. During the delay an intermediate of rhodopsin, N-Retinylidene Opsin (NRO440), that precedes the hydrolysis of the bleached chromophore from the opsin and that is associated with acidic conditions was observed. This intermediate was not observed in non-diabetic mice. The delay in rhodopsin regeneration of the diabetic mice was partially eliminated, and the relative concentration of NRO440 was decreased, when the internal pH of the rod photoreceptor was raised by modifying the perfusate composition.

Conclusions: Following a bleach, both genetic and streptozotocin diabetic mice exhibited abnormalities in rhodopsin regeneration. When studied at moderate bleaching levels with animals that were moderately diabetic, both groups of diabetic mice exhibited a delay in the start of the rhodopsin regeneration. The delay appears to be caused by the formation of an acid intermediate of the bleached rhodopsin resulting from acid conditions within the rod photoreceptors.