James v Jester
Professor of Biomedical Engineering
Jack H. Skirball Endowed Research Chair
|Cornea, Ocular Surface, Meibomian Glands|
Jack H. Skirball Endowed Research Chair.
Senior Scientific Investigator Award, Research to Prevent Blindness, Inc.
Association for Research in Vision and Ophthalmology Gold Fellow
Career Achievement Award, Ocular Toxicology, Society of Toxicology
The Ocular Surface, Laboratory Science Editor
Investigative Opthalmology & Visual Science, Editorial Board Member
Cutaneous and Ocular Toxicology, Editorial Board Member
Cornea, Editorial Board Member
National Eye Institute, Review Panel Member
Ocular Pathology, Doheny Eye Foundation, Los Angeles, California.
Experimental Ocular Pathology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Meibomian Gland Dysfunction
The long-term goal of this project is to understand the mechanism of age-related meibomian gland dysfunction (MGD) and evaporative Dry Eye. Recently we have shown that mouse and human meibomian glands undergo specific age-related changes including decreased acinar cell proliferation, acinar atrophy, and altered peroxisome proliferator-activated receptor gamma (PPAR gamma) localization from cytoplasmic-vesicluar/nuclear in young to nuclear in old mice and humans. Since PPAR is a lipid sensitive, nuclear receptor implicated in regulating adipocyte and sebocyte differentiation and lipogenesis, our findings suggest that PPAR may be involved in modulating meibomian gland differentiation during aging. Based on these findings we propose that aging of the meibomian gland may result in down-regulation of PPAR? leading to decreased meibocyte differentiation and lipid synthesis, gland atrophy, and a hyposecretory MGD. Currently, there is a MAJOR GAP in knowledge regarding the role of PPAR in meibomian gland function. To test this hypothesis we have develop novel imaging and cell culture systems to assess gland volume, lipid synthesis and their regulation by PPAR?. Using non-linear optical (NLO) microscopy and array tomography we have volumetrically reconstructed the mouse meibomian gland and measured total, cellular and lipid volumes in young and old glands. Preliminary studies suggest that atrophy of aging meibomian glands involves a marked loss in the lipid volume suggesting decreased meibocyte differentiation. Additionally, we have used coherent anti-stokes raman spectroscopy (CARS) to identify the regional lipid profiles within the meibomian gland and have tentatively shown that there is an age-related change in the maturation of meibomian gland lipids moving from the acini into the duct. Furthermore, we have developed an SV40 immortalized mouse meibocyte cell line that synthesizes lipids and expresses PPAR. Using these novel tools we propose the following Specific Aims. (1). Establish the age-related changes in PPAR localization and associated gene expression patterns by quantifying the subcellular localization, post-translational modification and downstream response gene expression patterns in the mouse and human meibomian gland. (2) Determine the effects of aging on the meibomian gland by quantifying the volume and lipid synthesis using NLO microscopy and array tomography to volumetrically reconstruct the meibomian gland and CARS to assess regional changes in lipid components present in the acini, ductule and duct of the mouse and human meibomian gland. (3) Assess the effects of natural and synthetic PPAR ligands on lipid synthesis by quantifying the subcellular localization, post-translational modification and downstream response gene expression patterns in cultured mouse meibocytes. (4) Measure the effect of PPAR ligands on meibocyte differentiation in vivo by quantifying the changes in PPAR expression, meibocyte proliferation, gland volume and lipid synthesis in young and old mouse meibomian glands.
|Publications||Winkler M, Chai D, Kriling S, Nien CJ, Brown DJ, Juhasz T, Jester JV: Non-linear optical macroscopic assessment of 3-D corneal collagen organization and axial biomechanics. Invest Ophthalmol Vis Sci 52:8818-8827, 2011. PMCID:PMC3230904.|
|Myrna KE, Mendonsa R, Russell P, Pot SA, Liliensiek SJ, Jester JV, Nealey PF, Brown D, Murphy CJ: Substratum topography modulates corneal fibroblast to myofibroblast transformation. Invest Ophthalmol Vis Sci 53:811-816, 2012. PMCID: PMC3317421.|
|Jester JV, Brown DJ, Pappa A, Vasiliou V: Myofibroblast differentiation modulates keratocyte crystallin protein expression, concentration and cellular light scattering. Invest Ophthalmol Vis Sci 53:770-778, 2012. PMCID:PMC3317419.|
|Jester JV, Nien CJ, Vasiliou V, Brown DJ: Quiescent keratocytes fail to repair MMC induced DNA damage leading to the long-term inhibition of myofibroblast differentiation and wound healing. Mol Vis 18:1828-1839, 2012. PMCID:PMC3398499|
|Jester JV: Corneal crystallins and cellular transparency. Sem Cell & Devel Biol 19:82-93, 2008.|
|Morishige N, Kesler-Diaz A, Wahlert AJ, Kurtz R, Juhasz T, Sarayba M, Jester JV: Corneal response to femtosecond laser photodisruption in rabbits. Exp Eye Res 86: 835-843, 2008.|
|Farid M, Morishige N, Lam L, Wahlert A, Steinert RF, Jester JV: Detection of corneal fibrosis following excimer laser surface ablation (PRK) using second harmonic generated (SHG) signals. Invest Ophthalmol Vis Sci 49:4377-4383, 2008.|
|Jester JV, Lam L, Wahlert A: Assessing ocular irritation potential using a modified ex vivo rabbit eye test. Journal of Toxicology, Cutan Ocul Toxicol 28:32-26, 2009.|
|Nien CJ, Paugh JR, Massei S, Wahlert AJ, Kao WW, Jester JV: Age-related changes in the meibomian gland. Exp Eye Res (in Press)|
|Morishige N, Nishida T, Jester JV: Second harmonic generation for visualizing three-dimensional structure of the corneal collagen lamellae. Cornea (in Press)|
|Jester JV, Brown DJ: Peroxisome proliferator-activated receptor-gamma (PPAR?) and meibomian gland dysfunction. Ocular Surface (in Press). PMCID:PMC in progress|
|Chen Y, Thompson DC, Koppaka V, Jester JV, Vasiliou V: Ocular aldehyde dehydrogenases: Protection against ultraviolet damage and refractory properties for vision. Prog Ret Eye Res d2012.|
|Parfitt GJ, Kie Y, Reid KM, Dervillez X, Brown DJ, Jester JV: A novel immunofluorescent computed tomography (ICT) method to localise and quantify multiple antigens in large tissue volumes at high resolution. PLosOne 7:e53245, 2012.|
|Chai D, Juhasz T, Brown DJ, Jester JV: Non-linear optical (NLO) collagen cross-linking and mechanical stiffening: A possible photodhynamic therapeutic approach to treating corneal ectasia. Journal of Biomedical Optics (in Press).|
|Grants||Age-Related Meibomian Gland Dysfunction, funded by the National Eye Institute.|
|Novel Role of corneal Crystallins as Modulators of Cell Growth and Transparency, funded by the National Eye Institute.|
Association for Research in Vision and Ophthalmology
International Society for Eye Research
American Society for Cell Biology
Experimental Pathology (PTH)
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=5668|