Key result
A Japanese patient with Danon disease manifested cone dystrophy, and molecular studies showed that LAMP2 knockdown in retinal pigment epithelium cells reduced autophagosome formation.
Why the study?
Danon disease can cause retinopathy, but the pathophysiological contribution of LAMP2 mutation to retinal dysfunction remains unclear.
Does LAMP2 dysfunction contribute to the pathogenesis of retinopathy in Danon disease?
Case Report (n=1)
Does LAMP2 dysfunction contribute to the pathogenesis of retinopathy in Danon disease?
LAMP2 plays an important role in autophagosome formation in retinal pigment epithelium, providing insight into the pathogenesis of Danon disease retinopathy.
Danon disease may feature cone dystrophy; hypothesis-generating for LAMP2 autophagy in retina and needs prospective confirmation.
Introduction: Lysosome-associated membrane protein 2 plays an important role in autophagy and lysosomal function and its mutation is responsible for pathogenesis of Danon disease, which can cause retinopathy, though its pathophysiological contribution to retinal dysfunction remains unclear. The purpose of our research is to report the first case of Japanese Danon disease retinopathy and to understand how LAMP2 dysfunction contributes to pathogenesis of retinopathy. Methods: One case underwent ophthalmic examination including slit-lamp exam, fundus imaging, visual field testing, and electroretinogram. In molecular biological study, relative messenger RNA expression levels of three splicing variants of Lamp2 or LAMP2 in wild type mouse retina and retinal pigment epithelium, human retinal pigment epithelium cell line adult retinal pigment epithelium-19 were quantified. LAMP2 was knocked down by small interfering RNA in adult retinal pigment epithelium-19 and its effect to LC3, an autophagy marker, was assessed by Western blotting. Intracellular localization of LAMP2 and LC3 in untreated and LAMP2-knocked-down adult retinal pigment epithelium-19 was analyzed by confocal microscopy. Results: Our case manifested cone dystrophy in both eyes. In mice, expression of Lamp2a and Lamp2b was significantly higher in retinal pigment epithelium than that in neural retina. Expression of Lamp2a and Lamp2b were significantly higher than that of Lamp2c in mouse retinal pigment epithelium. Adult retinal pigment epithelium-19 cells showed similar LAMP2 expression pattern to mouse retinal pigment epithelium. LAMP2 knockdown in adult retinal pigment epithelium-19 reduced LC3-II amount and the number and size of autophagosome. Discussion: We report a Japanese case of Danon disease retinopathy, and our study implies that LAMP2 plays an important role in autophagosome formation in retinal pigment epithelium.
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Fukushima et al. (2019) conducted a case report in Danon disease retinopathy (n=1). LAMP2 mutation/knockdown vs. Wild type/untreated cells was evaluated on Clinical manifestation and autophagosome formation. A Japanese patient with Danon disease manifested cone dystrophy, and molecular studies showed that LAMP2 knockdown in retinal pigment epithelium cells reduced autophagosome formation.
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