Authors
S Patricia Becerra
Published in
Bioscience reports. Volume 46. Issue 7. Jul 22, 2026.
Abstract
Photoreceptors are highly specialized neurons that depend on continuous membrane renewal and tightly regulated lipid homeostasis to maintain their visual function. Age-associated disruptions of these processes increase cellular stress and contribute to photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a potent neuroprotective factor in the retina, and the identification of its receptor, PEDF-R (PNPLA2), has provided key mechanistic insight into how PEDF signaling is coupled to lipid metabolism. The present review examines the molecular and cellular mechanisms underlying PEDF-R function in photoreceptors and the retinal pigment epithelium (RPE). PEDF-R acts as a multifunctional enzyme with phospholipase and lipase activities that link extracellular PEDF binding to intracellular lipid remodeling. Through these activities, PEDF-R has been associated with processes essential for photoreceptor survival such as membrane phospholipid turnover, mitochondrial integrity, calcium homeostasis, and redox balance. In addition, PEDF-R contributes to retinoid metabolism and lipid processing associated with outer-segment renewal in the RPE. We further discuss how disruption of the PEDF-PEDF-R pathway impairs lipid homeostasis, promotes oxidative and inflammatory stress, and increases susceptibility to age-related retinal degeneration. These insights position PEDF-R as a key contributor to photoreceptor homeostasis and a potential therapeutic target for preserving retinal function in aging and disease.
PMID:
42423603
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.
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