A5013066652- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- melanin and skin pigmentation
- CRISPR and Genetic Engineering
- Genetic and Kidney Cyst Diseases
- Neuroscience and Neural Engineering
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Hearing, Cochlea, Tinnitus, Genetics
- CAR-T cell therapy research
- Connexins and lens biology
- Corneal Surgery and Treatments
- Biochemical Analysis and Sensing Techniques
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Head and Neck Surgical Oncology
- Venomous Animal Envenomation and Studies
- Calpain Protease Function and Regulation
- Spaceflight effects on biology
- Amyotrophic Lateral Sclerosis Research
- 3D Printing in Biomedical Research
- Biomedical Research and Pathophysiology
- Erythrocyte Function and Pathophysiology
University of California, Los Angeles
2009-2020
University of California, Santa Barbara
2017-2018
Doheny Eye Institute
2009-2015
University of Coimbra
2004-2015
Allen Institute
2014
University of California, San Diego
2009-2011
Imperial College London
2004-2009
NIHR Imperial Biomedical Research Centre
2004-2006
The degradation of phagosomes, derived from the ingestion photoreceptor outer segment (POS) disk membranes, is a major role retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved apical region RPE. Live-cell imaging showed that bidirectionally along microtubules in RPE cells, kinesin-1 light chain 1 (KLC1) remaining associated both directions during pauses. Lack KLC1 did not inhibit phagosome speed, but run length...
Pathways of melanosome biogenesis in retinal pigment epithelial (RPE) cells have received less attention than those skin melanocytes. Although the bulk melanin synthesis RPE occurs embryonically, it is not clear whether adult continue to produce melanosomes. Here, we show that progression from pmel17-positive premelanosomes tyrosinase-positive mature melanosomes largely complete before birth. Loss functional Rab38 "chocolate" (cht) mouse causes dramatically reduced numbers RPE, contrast mild...
The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements fish and amphibians. In mammals, are more subtle appear be regulated by Rab27a GTPase unconventional myosin, Myosin VIIa (MyoVIIa). Here we address hypothesis that a recently identified Rab27a- MyoVIIa-interacting protein, Myrip, promotes formation of functional tripartite complex. heterologous cultured cells, all three proteins...
Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In retina, majority of is retinal pigmented epithelium (RPE), where many reactions visual retinoid cycle take place. We have observed that retinas Myo7a- mutant mice are resistant to acute light damage. exploring basis this resistance, we found lower levels RPE65, RPE isomerase has key role cycle. show for first time RPE65 normally undergoes light-dependent translocation become more concentrated central...
Dysfunction of the retinal pigment epithelium (RPE) is implicated in numerous forms degeneration. The readily accessible environment eye makes it particularly suitable for transplantation RPE cells, which can now be derived from autologous induced pluripotent stem cells (iPSCs), to treat For become feasible clinic, patient-specific somatic should reprogrammed iPSCs without introduction reprogramming genes into genome host cell, and then subsequently differentiated that are well characterized...
In the vertebrate retina, light is detected by outer segments of photoreceptor rods and cones, which are highly modified cilia. Like other cilia, have no protein synthetic capacity depend on proteins made in cell body for their formation maintenance. The mechanism transport into segment not fully understood but intraflagellar (IFT) thought to be a major moving from cilium. case cells, high density receptors disk turnover that occurs daily necessitates much higher rates than would required...
Due to extensive elaboration of the photoreceptor cilium form outer segment, axonemal transport (IFT) in photoreceptors is extraordinarily busy, and retinal degeneration a component many ciliopathies. Functional loss heterotrimeric kinesin-2, major anterograde IFT motor, causes mislocalized opsin, followed by rapid cell death. Here, we have analyzed nature protein mislocalization requirements for death kinesin-2-mutant rod photoreceptors. Quantitative immuno EM showed that opsin accumulates...
Melanoregulin (MREG), the product of Mreg(dsu) gene, is a small highly charged protein, hypothesized to play role in organelle biogenesis due its effect on pigmentation dilute, ashen, and leaden mutant mice. Here we provide evidence that MREG required lysosome-dependent phagosome degradation. In Mreg(-/-) mouse, show loss function results accumulation delayed degradation engulfed material. Over time, mouse retinal pigment epithelial cells accumulate lipofuscin component, A2E. MREG-deficient...
purpose. To investigate the expression of harmonin in mouse retina, test for ultrastructural and physiological mutant phenotypes retina an Ush1c mouse, define detail retinal phenotype human USH1C. methods. Antibodies were generated against harmonin. Harmonin isoform distribution was examined by Western blot analysis immunocytochemistry. Retinas deaf circler (dfcr) mice, which possess Ush1c, analyzed microscopy electroretinography (ERG). Two siblings with homozygous 238_239insC (R80fs) USH1C...
Mutations in the head and tail domains of motor protein myosin VIIA (MYO7A) cause deaf-blindness (Usher syndrome type 1B, USH1B) nonsyndromic deafness (DFNB2, DFNA11). The domain binds to F-actin serves as MYO7A domain, but little is known about function domain. In a genetic screen, we have identified polka mice, which carry mutation (c.5742 + 5G > A) that affects splicing transcript truncates at C-terminal FERM inner ear, expression truncated severely reduced, leading defects hair cell...
Melanosomes are motile, light-absorbing organelles that present in pigment cells of the skin and eye. It has been proposed melanosome localization, both melanocytes retinal epithelium (RPE), involves capture from microtubule motors by an unconventional myosin, which dynamically tethers melanosomes to actin filaments. Recent studies with have questioned this cooperative model. Here, we test model RPE imaging associated labeled filaments microtubules, investigating roles different motor...
Myrip is a Rab27a and MyosinVIIa (MyoVIIa) linking protein that may regulate melanosome transport in the retinal pigment epithelium (RPE). also binds MyosinVa (MyoVa) vitro however it unclear whether this interaction of sufficient affinity to be physiologically relevant. Here, we addressed questions interacts with MyoVa cells molecular basis cellular activation MyoVIIa by Myrip. To answer these used skin melanocytes RPE as read-outs activity. We found recruits activates on melanosomes...
The current standard method to culture human limbal stem/progenitor cells (LSCs) in vitro is epithelial directly on a layer of murine 3T3 feeder (standard method). direct contact between and poses the potential risk incomplete removal after cross-contamination clinical applications. We present here novel three-dimensional (3D) sandwich which LSCs were separately cultured opposite sides porous membrane. Limbal form single-cell suspensions, cell clusters, tissue explants subjected or 3D...
Abstract Replacement of retinal pigment epithelium (RPE) cells by transplantation is a potential treatment for some degenerations. Here, we used combination invasive and noninvasive methods to characterize the structural functional consequences subretinal injection RPE cells. Pigmented from primary cultures were injected into albino mice. Recovery was monitored over 8 weeks fundus imaging, spectral domain optical coherence tomography (sdOCT), histology, electroretinography (ERG). sdOCT...
Cathepsin-D (Cat-D) is a major proteolytic enzyme in phagocytic cells. In the retinal pigment epithelium (RPE), it responsible for daily degradation of photoreceptor outer segments (POSs) to maintain homeostasis. Melanoregulin (MREG)-mediated loss capacity has been linked diminished intracellular Cat-D activity. Here, we demonstrate that MREG enhances secretion intermediate (48 kDa), resulting net enhancement extracellular These results suggest required homeostasis RPE and likely plays...