Photoreceptor disc incisures are formed as a safeguard to ensure the completion of disc enclosure

Abstract

Purpose : The first steps in vision take place within a stack of tightly packed disc-shaped membranes, or “discs”, located in the photoreceptor outer segment. In rods, discs are enclosed inside the outer segment and contain deep indentations called “incisures”. The presence of incisures has been documented across a wide variety of species, yet their biological role remains elusive. In this study, we sought to investigate the cellular and molecular mechanisms underlying incisure formation.

Methods : First, we combined traditional electron microscopy with three-dimensional electron tomography to analyze the spatiotemporal relationship between incisure formation and disc enclosure in wild-type mouse photoreceptors. Second, we employed a number of genetically manipulated mice and frogs to investigate the molecular players that control incisure formation. Third, we utilized a quantitative proteomic approach to determine the precise molar ratios amongst several outer segment proteins in wild type and mutant mouse models.

Results : Our ultrastructural analysis revealed that incisure formation takes place only after discs become completely enclosed. We further showed that incisure size is determined by the relative outer segment content of peripherin-2, a disc rim protein critical for the process of disc enclosure. While a high perpherin-2 content causes an increase in incisure size, a low content precludes incisure formation.

Conclusions : To explain these observations, we propose a model whereby normal rods express a modest excess of peripherin-2 over the amount required for complete disc enclosure in order to ensure that this important step of disc maturation is accomplished. Once the disc is enclosed, the excess peripherin-2 is deposited at the incisure. Ultimately, incisures are formed as a safeguard to ensure the completion of disc enclosure.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.