Role of Rho-A in Glaucoma

Jasleen Kaur

Narmada Jayasankar

Vijetha Vemulapalli

Outline

Open angle Glaucoma RhoA pathway and hypothesis CATPA

Open Angle Glaucoma

It can be defined as damage to the Optic nerve due to Increase in Intra ocular pressure (IOP)

Anatomy of the angle

Trabecular meshwork

Shields textbook of glaucoma-2005

Cornea

Retina

Cell cytoskeleton

Green: actinRed: mitochondriaBlue: nucleus

TM Cell Contractility

Aqueous humor regulation is done by TM cell contractility and re-alignment of pores.

There are two pathways that regulate TM contractility.

Ca dependent pathways And the Ca independent pathway. Rho-a protein is involved in the Ca

independent pathway.

General Function of Rho-A

Involved in the maintenance of tight junctions. Tight junctions are found in epithelial cells

and all cells where there is a separation or demarcation into different regions.

If the Rho-A pathway does not function properly in the eye, it causes Glaucoma.

Ca independent pathway

GDI

GAP

GEF

GTP GDP

P

RhoA-GDP

Plasma membrane

ContractionRelaxation MLC pMLC

M20

MYPT1

PP1C

Active MLCP

M20

MYPT1

PP1C

Inactive MLCP

RhoA-GDP RhoA-GTP Rho kinase

CATPA

CATPA

Point Mutations

Point Mutations

References 1. http://biology.kenyon.edu/BMB/Chime2/

2002/rhoA/FRAMES/captxt.htm 2. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=165390 3. PDB, CATH, SCOP 4. http://ajpcell.physiology.org/cgi/content/full/275/3/C798 5.http: //www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1220893 6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14815 7. http://147.52.72.117/ijmm/2002/volume9/number6/563-570.pdf 8. http://apodaca2.dept-med.pitt.edu/PDFs/Rajasesekeran-TJs.pdf 9. www.ucl.ac.uk/ioo/research/greenwood.htm