Stargardt disease is caused by mutations in the
ABCA4 gene located on the short arm of chromosome 1.
4 The protein plays an important role in the recycling of vitamin A in the visual cycle. It is located in the outer segment (OS) disc membranes of both rod and cone photoreceptors.
5–9 N-retinylidene-phosphatidylethanolamine (NRPE), formed by the binding of all-
trans-retinal to the phospholipid phosphatidylethanolamine (PE), is removed from the outer segment disc membranes by normally functioning ABCA4 protein.
7,10,11 ABCA4 insufficiency, as occurs in STGD1, augments the build-up of NRPE in the disc space and thus allows binding of a second molecule of all-
trans-retinal to NRPE, leading to increased formation of A2E and related bisretinoid molecules,
12 which are the only known components of lipofuscin. Lipofuscin subsequently accumulates in the RPE due to OS disc shedding and phagocytosis and can be toxic to the RPE through a number of mechanisms.
13 Histopathological examination of eyes from patients with STGD1 has demonstrated large RPE cells densely packed with granules that exhibit the structural and biochemical (periodic acid-Schiff positive) characteristics of lipofuscin.
14–17 Studies of fundus autofluorescence (AF), an intrinsic signal originating from RPE lipofuscin,
18 have corroborated these histopathological findings, suggesting a greater accumulation of lipofuscin in
ABCA4 retinopathy in comparison with controls.
19–21 In a previous study, fundus AF was measured spectrophotometrically at a position 7° temporal to the fovea using an excitation wavelength of 510 nm.
19 Autofluorescence intensity was found to be ∼3-fold higher in STGD1 patients than in control subjects of the same age. The emission spectra of fundus AF in STGD1 patients was similar in shape to normal subjects, there being a broad emission maximum in the 620- to 640-nm range.
18