ARMD: ANALYSIS OF GENE EXPRESSION IN THE HUMAN RETINA

TITLE: AGE RELATED MACULAR DEGENERATION: ANALYSIS OF GENE EXPRESSION IN THE HUMAN RETINA
SPONSOR:

Global Ophthalmology Awards Program from BAYER

CO-SPONSOR:
TIMEFRAME: November 2012 – November 2013 (1 Year)
THEME: Age-Related Macular Degeneration
STATUS: CLOSED
GRANT AMOUNT: 25.000 US$
FBOV ROLE: Coordinator
PARTNERS INVOLVED: University of Parma (Italy)
P.I. : Dr. Diego PONZIN, MD

SUMMARY: A genetic origin of the Age-Related Macular Degeneration (ARMD) has been inferred (genes of the immune system, H-factor of the complement, etc.), but related studies have so far been carried out in the genome of peripheral blood cells and never in ocular tissues. The reasons behind this are the huge practical difficulties encountered in obtaining human retina/choroid samples for research purposes, and in rapidly processing the genetic material extracted from these samples.

 

OBJECTIVES/SCOPE :The aim of this research project is to study potential alterations in gene expression directly in the retinal/choroid tissues of subjects affected by ARMD.

 

SUMMARY OF METHODS: Human retina and choroid will be harvested from the donor eyes, which corneas will be used for transplantation. Half of each sample will be analysed for histological research of signs of ARMD (presence of “drusen” in dry ARMD, and of vessels from the choroid in exudative ARMD), with the other half being used for RNA extraction. Preliminary results have already validated protocols for extraction of good quality RNA (RIN>8) from retina/choroid samples of human eye bulbs (Mora P et al., Retina-The Journal of Retinal and Vitreous Diseases 2010; 30: 1555). Gene expression in affected subjects will be evaluated by means of microarray (Microarray Scanner System G2565AA), and compared with that of healthy donors. The identification of one or more genes which are “up”- or “down”-regulated might allow us to identify alterations in the molecular patterns of diseased tissues.

 

EXPECTED RESULTS: So far, no gene expression studies have directly involved the tissues affected with ARMD, i.e. the human retina and choroid. Microarray-based analyses will allow identifying which genes are mostly deregulated in ARMD, and they might therefore provide a new key to the pathogenesis of the disease. It is worth remembering that the finding of significantly increased levels of VEGF in the vitreous humor of patients with neo-vascular ARMD has been the basis for the therapeutic application of anti-VEGF. Our findings might therefore suggest new potential pharmaceutical targets for patients with ARMD or identify further genes linked to the risk of having/developing ARMD.

 

PUBLICATIONS:

 

ABSTRACTS/POSTERS TO CONFERENCES:

 

Further details can be found at the following link: http://www.bayer-ophthalmology-awards.com/html/b-about-d.html

 

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