Lipofuscin fluorophore inhibits lysosomal protein degradation and may cause early stages of macular degeneration.
One of the autofluorescent compounds that accumulates within the lipofuscin granules of the human retinal pigment epithelium (RPE) has now been identified as a quaternary nitrogen-containing cationic amphiphile (the bis-retinoid pyridinium salt, A2-E). Experimental evidence suggests that it may be responsible for lipofuscinogenesis in the RPE through its ability to inhibit lysosomal proteolysis. Furthermore, it may be involved in the events that trigger the changes leading to age-related macular degeneration (AMD), the leading cause of untreatable blindness in the elderly. It is suggested that if similar weakly basic nitrogenous compounds or cationic amphiphiles arise in reactions between amines and aldehydes in other tissues, a "self-assembling lysosomotropic amine" mechanism may provide an alternative explanation for lipofuscinogenesis those cell types as well.
Eldred
G E
GE
Augenklinik, Universitätsspital Zürich, Switzerland.
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000818:Animals; D002648:Child; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism / Q000494:pharmacology*; D008268:Macular Degeneration / Q000209:etiology* / Q000503:physiopathology; D008875:Middle Aged; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000502:physiology; D012168:Retinal Pigments / Q000378:metabolism / Q000502:physiology
D008062:Lipofuscin; D011506:Proteins; D012168:Retinal Pigments; C018589:lysosomal proteins