Retinal degeneration is caused by a group of progressive neurological disorders that may arise from genetic mutations and environmental/pathological damage, leading to visual impairment or visual loss. Common retinal degenerative diseases in adults include age-related macular degeneration (AMD), glaucoma, diabetic retinopathy, and retinitis pigmentosa. The prevalence of these diseases ranges from millions to hundreds of millions [1,2,3,4] and is projected to increase with aging global population.

Current treatments for retinal degeneration include cell transplantation, drug delivery, and gene therapy [5,6,7]. Gene therapy has produced transformational knowledge in retinal treatments by examining the transient expression of different types of enzymes, transcription factors, and genes that mediate retinal development and function. These factors are currently highly examined as potential therapeutics for retinal repair and regeneration. Moreover, genetic engineering is an emerging research field, in which direct manipulation of one or more genes can be used to determine their function or role. For example, gene knockdown is often utilized to determine the role of a certain gene by observing how the function or development of the retina is altered through the loss-of-function of the gene.

Our lab recently developed a computational pipeline [8] was used to identify functional genes significant to development, as well as expression patterns of a variety of genes in the retina. Many of these genes that showed peak expression levels were novel in regard to their function in the retina, including Lysosomal-associated Transmembrane 4-Beta (Laptm4b), Pde8b, and Nr1h4. To further confirm a functional role of Laptm4b during retinal development, immunohistochemistry was employed to detect its expression in the developing mouse retina at postnatal day 14 (P14). Immunofluorescence staining revealed that the expression of Laptm4b was concentrated in the mouse outer segment (OS) of the retina, whose development reaches peak levels around P14 [9], and overlaps with the staining pattern of the known OS marker, Rhodopsin. This suggests that Laptm4b function may be important, specifically, for the development of the OS of the retina.

Laptm4b belongs to a membrane spanning lysosomal LAPTM family of proteins [10, 11] and has been implicated in a number of functions and roles within the human body. Some of these roles/functions include membrane composition [12], exosome transport [13], tumor development [11, 14, 15], sphingolipid regulation [12, 13], and autophagy [10, 14, 15]. Previous findings regarding Laptm4b include: (1) affecting the subcellular distribution of cytotoxic drugs [10], (2) regulating epidermal growth factor receptor signaling by acting on its lysosomal sorting, degradation, and autophagy initiation [10, 14, 15], (3) being a novel oncogene that promotes tumorigenesis and may be a biomarker for several cancers [11, 14, 15], (4) being a determinant of glycosphingolipid profile and membrane properties of small extracellular vesicles for cellular transport and waste removal [12], and (5) association with molecules within the sphingolipid network for exosome release, such as ceramide (Cer) [12, 15].

While Laptm4b has been studied in many research areas, such as exosome release and cancer research, its functional role in the retina has been yet to be examined. Sphingolipids have been recently associated with many retinal degenerative diseases including AMD and glaucoma, and recent findings have linked Laptm4b to sphingolipids. Autophagy has also been implicated in retinal development and associated with Laptm4b. These findings have led to the belief that Laptm4b may be involved in the retina during the developmental stages.

Building a connection between the role(s) of Laptm4b on retinal development will provide novel findings regarding OS development, as well as retinal degeneration. This newfound link may contribute to the efforts toward developing treatments and/or cures for vision loss and blindness caused by retinal degenerative diseases.