Neat!

Joanne Matsubara

Professor
Department of Ophthalmology and Visual Sciences
Assistant Director, Centre for Macular Research

 

Email: jms...@interchange.ubc.ca
Phone: 604 822-3941

Web pages: Lab webpage

 

Education

Keywords

  • Macular degeneration
  • Amyloid beta
  • Proliferative vitreoretinopathy

Research Interests

1. Age related macular degeneration (AMD)

Recent studies have provided insights into the role of the complement system and retinal inflammation in the pathogenesis of AMD. Several groups have identified a polymorphism in the complement factor H (CFH) gene that is linked to an increased risk of developing AMD. Human factor H is an inhibitory regulator of the ‘alternate’ pathway of complement system. Mutations in this gene have been suggested to promote complement activation, leading to chronic inflammation in the retina. It is hypothesized that chronic inflammation in the retina may result in the recruitment of macrophages and microglia cells. Unfortunately, these cells also release their own toxins, including reactive oxygen species, which injure the normal retinal tissues as well. Oxidative injury to normal retinal tissues may promote AMD disease progression by initiating an abnormal angiogenic or wound healing response that may promote choroidal neovascularization, a characteristic of the exudative form of AMD.

While the complement system has been implicated in the pathogenesis of AMD, it is not known what causes or triggers the complement system to go awry in AMD. At present, there are several candidate molecules that may activate or trigger the complement system in AMD. Amyloid beta, an activator of the complement system, is a constituent of drusen, the hallmark extracellular deposit in the dry form of AMD. Amyloid beta deposits in drusen, like the amyloid beta deposits in senile plaques of Alzheimer’s disease, are associated with activated complement proteins and cell injury.

Research in the Matsubara Lab focuses on amyloid beta, a toxic peptide that has been implicated in retinal inflammation, and the role that amyloid beta may play in gene expression of the retinal pigment epithelial (RPE) cell. It is hypothesized that amyloid beta is one of the triggers of the complement pathways that causes chronic inflammation in the retina. Local chronic inflammation in the retina may alter gene expression in the RPE cells and choroidal endothelial cells (CEC). These gene expression changes may initiate RPE-induced choroidal neovascular events leading to the exudative or wet form of AMD.

2. Proliferative Vitreoretinopathy (PVR)

Proliferative vitreoretinopathy is the most common cause for failure of retinal detachment surgery and is characterized by the formation of fibrocellular epiretinal or subretinal membranes. Studies have shown that PVR membranes are composed of various cell types, including retinal pigment epithelial, glia, fibroblast, inflammatory macrophage and lymphocyte types. These membranes contract causing retinal tears and detachments. The incidence of PVR remains at approximately 5-10% of retinal detachments that come to surgery. There is no known preventative therapy, and the current intervention is surgical removal.

There is both indirect and direct evidence supporting the idea that growth factors play a key role in PVR. We are interested in understanding the stage specificity of growth factor expression during the development of PVR. Several of our studies have shown that connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and hepatocyte growth factor (HGF) are expressed at different stages of PVR development.

Research in the Matsubara Lab focuses on the molecular mechanisms associated with these growth factors, and their receptors on retinal pigment epithelial cells in vitro and in vivo. Translational studies are aimed at identifying molecular targets for PVR treatment strategies.


Selected Publications

 Cui J., Maberley D., Samad A., Ning A., Matsubara J., Baciu P. Expression of Integrins on Human Choroidal Neovascular Membranes. Journal of Ocular Biology, Diseases and Informatics, in press.

 Cui J., Lei H, Samad A., Basavanthappa S., Maberley D., Matsubara J., Kazlauskas A. PDGF Receptors Are Activated in Human Epiretinal Membranes. Experimental Eye Research. Experimental Eye Research; Nov 8 [Epub ahead of print].

Cui J.Z., Wang X.F., Hsu L., Matsubara J.A. Inflammation induced by Photocoagulation Laser is Minimized by Copper Chelators. Lasers in Medical Sciences, June 20 [Epub ahead of print].

Ning A., Cui J.Z., To E., Hsiao Ashe K., Matsubara J.A. Amyloid Beta Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease. Investigative Ophthalmology & Visual Science 49(11):5136-43.

Ning A.L., Cui J.Z., Maberley D., Ma P., Matsubara J. Expression of Integrins in Human Proliferative Diabetic Retinopathy Membranes. Canadian Journal of Ophthalmology 43(6):683-688.

Seth A., Cui J., To E., Kwee M., Matsubara J. Complement-associated deposits in the human retina. Investigative Ophthalmology & Visual Science 49(2):743-50.

Cui JZ, Chiu A, Maberley D, Ma P, Samad A, and Matsubara JA. Stage Specificity of Novel Growth Factor Expression During Development of Proliferative Vitreoretinopathy. Eye Feb; 21(2):200-8.

Maberley, D., Cui, J.Z., Matsubara, JA. Vitreous Leptin Levels in Retinal Disease. Eye Jul; 20(7):801-4.

Wang XF, Cui JZ, Prasad SS and Matsubara JA. Altered Gene Expression of Angiogenic Factors Induced by Calcium-Mediated Dissociation of Retinal Pigment Epithelial Cells. Investigative Ophthalmology and Visual Science 46: 1508-1515.

Wang XF, Cui JZ, Nie WJ, Prasad SS and Matsubara JA. Differential Gene Expression of Early and Late Passage Retinal Pigment Epithelial Cells. Experimental Eye Research 79:209-221.

Cui J.Z., Wong C.A., Ma P., Potter M.J., Maberley D., To E.C., Samad A., and Matsubara J.A. Immunolocalization of Mmps In Epiretinal Membranes From Proliferative Vitreoretinopathy (PVR). American Society of Retina Specialists Online Journal June 16; 3(1).

Cui J.Z., Hornan D., Potter M.J., Hinz B.J., Greve M.D.J., Samad A., To E., Au E., Matsubara J.A. Expression of Neuropilin-1 in Choroidal Neovascular Membranes. Can J Ophthalmol 38(1):41-45.

Other

 

 

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