A5111746832- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Retinoids in leukemia and cellular processes
- Photoreceptor and optogenetics research
- Connexins and lens biology
- Retinal Imaging and Analysis
- Ion Transport and Channel Regulation
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Complement system in diseases
- Retinopathy of Prematurity Studies
- Photochromic and Fluorescence Chemistry
- Barrier Structure and Function Studies
- Antioxidant Activity and Oxidative Stress
- Neuroscience and Neuropharmacology Research
- Biomedical Research and Pathophysiology
- Corneal Surgery and Treatments
- Caveolin-1 and cellular processes
- Signaling Pathways in Disease
- Glycosylation and Glycoproteins Research
- Retinal and Optic Conditions
- CCD and CMOS Imaging Sensors
- Pluripotent Stem Cells Research
- Biotin and Related Studies
- Nuclear Receptors and Signaling
University of California, Los Angeles
2007-2024
University of California, Berkeley
2024
Doheny Eye Institute
2008-2020
Southern California Eye Institute
2019
Springer Nature (Germany)
2014
McGill University
1995-2013
Ophthalmology Associates (United States)
2008
UCLA Health
2007
Thomas Jefferson University
2005
Cornell University
2005
Vitamin A has diverse biological functions. It is transported in the blood as a complex with retinol binding protein (RBP), but molecular mechanism by which vitamin absorbed cells from A-RBP not clearly understood. We identified bovine retinal pigment epithelium STRA6, multitransmembrane domain protein, specific membrane receptor for RBP. STRA6 binds to RBP high affinity and robust uptake activity complex. widely expressed embryonic development adult organ systems. The represents major...
Abstract A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in but not normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T therapy target treat patients with cutaneous and rare melanoma subtypes unresponsive immune checkpoint blockade. TYRP1 primarily located intracellularly the melanosomes, small fraction being trafficked via vesicular transport. We develop...
We introduce a human retinal pigmented epithelial (RPE) cell-culture model that mimics several key aspects of early stage age-related macular degeneration (AMD). These include accumulation sub-RPE deposits contain molecular constituents drusen, and activation complement leading to formation deposit-associated terminal complexes. Abundant are rich in apolipoprotein E (APOE), prominent drusen constituent, formed by RPE cells grown on porous supports. Exposure serum results selective,...
Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and most common cause vision among elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) human-induced pluripotent (hiPSCs), may provide an abundant donor source for generating RPE in cell replacement therapies. Despite a significant amount research on deriving functional from various sources, it still unclear whether stem-cell-derived fully mimic...
purpose. Dietary supplementation with vitamin A is sometimes prescribed as a treatment for retinitis pigmentosa, group of inherited retinal degenerations that cause progressive blindness. Loss-of-function mutations in the ABCA4 gene are responsible subset recessive pigmentosa. Other mutant alleles related diseases, cone-rod dystrophy, and Stargardt macular degeneration. Mice knockout mutation abca4 massively accumulate toxic lipofuscin pigments pigment epithelium. Treatment these mice...
Integrity of retinal pigment epithelial cells is necessary for photoreceptor survival and vision. The essential omega-3 fatty acid, docosahexaenoic attains its highest concentration in the human body photoreceptors assumed to be a target lipid peroxidation during cell damage. We have previously shown, contrast, that acid also precursor neuroprotectin D1 (NPD1), which now we demonstrate, acts against apoptosis mediated by A2E, byproduct phototransduction becomes toxic when it accumulates...
Accumulation of vitamin A-derived lipofuscin fluorophores in the retinal pigment epithelium (RPE) is a pathologic feature recessive Stargardt macular dystrophy, blinding disease caused by dysfunction or loss ABCA4 transporter rods and cones. Age-related degeneration, prevalent elderly, strongly associated with mutations genes for complement regulatory proteins (CRP), causing chronic inflammation RPE. Here we explore possible relationship between accumulation activation vivo. Using abca4−/−...
Significance Recessive Stargardt macular degeneration (STGD1) and a subset of cone–rod dystrophies are caused by mutations in the Abca4 gene. The ABCA4 protein is flippase photoreceptor cells that helps eliminate retinaldehyde, toxic photoproduct vision. Here we found additionally present retinal pigment epithelium (RPE) mice at approximately 1% its abundance neural retina. Genetically modified express RPE but not showed partial rescue both lipofuscin accumulation observed −/− STGD1...
Proton-coupled monocarboxylate transporters (MCT) MCT1, MCT3, and MCT4 form heterodimeric complexes with the cell surface glycoprotein CD147 exhibit tissue-specific polarized distributions that are essential for maintaining lactate pH homeostasis. In parenchymal epithelia of kidney, thyroid, liver, MCT/CD147 heterocomplexes localized in basolateral membrane where they transport out or into depending on metabolic conditions. A unique distribution is found retinal pigment epithelium (RPE),...
Aquaporin (AQP) is a hexahelical integral membrane protein that functions as constitutive channel for water and regulated cations in fluid transporting tissues, including many the eye. Although AQP1 has been cloned from cDNA library prepared cultures of retinal pigment epithelial (RPE) cells isolated human fetal tissue, three separate studies failed with various immunochemical techniques to detect adult or rat RPE preparations. The purpose this study was examine specifically expression...
The first event in light perception is absorption of a photon by the retinaldehyde chromophore an opsin pigment rod or cone photoreceptor cell. This induces isomerization chromophore, rendering bleached insensitive to light. Restoration sensitivity requires chemical reisomerization via multistep enzyme pathway, called visual cycle, cells retinal epithelium (RPE). Interphotoreceptor retinoid-binding protein (IRBP) present extracellular space between photoreceptors and RPE. IRBP known bind...
We report generation of a mouse model in which the STRA6 gene has been disrupted functionally to facilitate study visual responses, changes ocular morphology, and retinoid processing under protein deficiency. METHODS.A null line, stra6 -/-, was generated.Western Blot immunocytochemistry were used determine expression protein.Visual responses morphological studies performed on 6-week, 5-month 10-month-old mice.The content eye tissues evaluated dark-adapted mice by high performance liquid...
Na,K-ATPase regulates a variety of transport functions in epithelial cells. In cultures human retinal pigment (RPE) cells, inhibition by ouabain and K + depletion decreased transepithelial electrical resistance (TER) increased permeability tight junctions to mannitol inulin. Electrophysiological studies demonstrated that the decrease TER was due an increase paracellular shunt conductance. At light microscopy level, this not accompanied changes localization junction proteins ZO-1, occludin,...
Visual perception begins with the absorption of a photon by an opsin pigment, inducing isomerization its 11-cis-retinaldehyde chromophore. After brief period activation, resulting all-trans-retinaldehyde dissociates from apoprotein rendering it insensitive to light. Restoring light sensitivity apo-opsin requires thermal re-isomerization via enzyme pathway called visual cycle in retinal pigment epithelial (RPE) cells. Vertebrates can see over 10(8)-fold range background illumination. This...
Age-related macular degeneration (AMD) is a common central blinding disease of the elderly. Homozygosity for sequence variant causing Y402H and I62V substitutions in gene complement factor H (CFH) strongly associated with risk AMD. CFH, secreted by many cell types, including those retinal pigment epithelium (RPE), regulatory protein that inhibits activation. Recessive Stargardt maculopathy another caused mutations ABCA4, transporter photoreceptor outer segments (OS) clears retinaldehyde...
CD147, a type I integral membrane protein of the immunoglobulin superfamily, exhibits reversed polarity in retinal pigment epithelium (RPE). CD147 is apical RPE contrast to its basolateral localization extraocular epithelia. This elicited our interest understanding sorting signals prototypic Madin-Darby canine kidney (MDCK) cells. The cytoplasmic domain has information but devoid well-characterized signals, such as tyrosine and di-leucine motifs. Hence, we carried out systematic...
Interphotoreceptor retinoid-binding protein (IRBP) secreted by photoreceptors plays a pivotal role in photoreceptor survival and function. Recently, D1080N mutation IRBP was found patients with retinitis pigmentosa, frequent cause of retinal degeneration. The molecular cellular bases for pathogenicity the are unknown. Here, we show that abolishes secretion results formation insoluble high weight complexes via disulfide bonds. Co-expression isomerase A2 regulates bond or introduction double...
To describe the pathology of AMD in eyes with geographic atrophy (GA) using confocal scanning laser ophthalmoscopy (SLO) blue light autofluorescence (BAF), and near-infrared (IR) AF to correlate it histology immunohistochemistry analysis at margins GA lesion.Enucleated, fixed from seventeen donors were imaged analyzed by BAF-SLO, IRAF-SLO, fundus macroscopy (FM). Tissue lesions was cut processed for resin embedding or cryosectioning fluorescence green far-red channels, assess markers...
Vitamin A has diverse biological functions and is essential for human survival at every point from embryogenesis to adulthood. its derivatives have been used treat diseases including vision diseases, skin cancer. Both insufficient excessive vitamin uptake are detrimental, but how transport regulated poorly understood. STRA6 a multitransmembrane domain cell-surface receptor mediates plasma retinol binding protein (RBP). can mediate both cellular influx efflux, what regulates these opposing...
Recessive Stargardt disease (STGD1) is an inherited retinopathy caused by mutations in the ABCA4 gene. The protein a phospholipid-retinoid flippase outer segments of photoreceptors and internal membranes retinal pigment epithelial (RPE) cells. Here, we show that RPE cells derived via induced pluripotent stem-cell from molecularly clinically diagnosed STGD1 patient exhibited reduced diminished activity compared to normal subject. Consequently, accumulated intracellular...