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OCULAR DEVELOPMENT AND NEUROBIOLOGYGROUP

OCULAR DEVELOPMENT AND NEUROBIOLOGY: RESEARCH OVERVIEW

Group Leader :

Prof. Michael A. Wride (Assistant Professor)

Introduction:

Work in the Ocular Development and Neurobiology research group is mainly concerned with the basic cellular, developmental and molecular genetic mechanisms that underlie the formation of the eye, an organ that Darwin described as one of his “Organs of Extreme Perfection and Complication” in 'The Origin of Species'.

Specifically, we are interested in the development and ageing of the lens and retina. Both are classic systems in developmental biology (e.g. Hans Spemann was awarded the 1935 Nobel Prize for Physiology or Medicine in part because of his work on lens induction. Furthermore, the study of the development of these essential components of the eye is highly relevant to gaining improved insights in to blindness caused by diseases such as cataract, glaucoma and age-related macular degeneration.

Techniques

We use molecular biology techniques to investigate gene expression including RT-PCR/QPCR, microarray analysis, RNASeq, Western blotting, immunofluoresence microscopy, laser scanning confocal microscopy, histology and manipulation of genes/proteins of interest in tissue and cell culture and in vivo.

The molecular basis of lens development, ageing and cataract:

We are interested in the development of the ocular lens. The lens is comprised of two cell types: the lens epithelium at the anterior, which contains a stem cell population, and the lens fibre cells, which are derived from the differentiation of lens epithelial cells (See Figure 1). In particular, we have been studying the development of the secondary lens fibres, which undergo a process of organelle loss, including loss of nuclei. This process is essential for lens transparency. In order to clear itself of organelles, the lens uses cell death or apoptosis signalling pathways and various proteases. It is becoming apparent that defects in this process can cause cataract. We are also interested in using the lens to gain insights into molecules that regulate both cell proliferation and cell death, such as the tumour suppressor p53 and its regulator Mdm2 (see Figure 2).

Cataract is a clouding of the lens of the eye, which impedes the passage of light to the retina causing low vision or complete blindness. It results from ageing of the lens and with mutations in lens development genes and is one of the priority eye diseases of the World Health Organisation (WHO). There is still no known means of preventing this and although it is quite successfully treatable by implanting artificial lenses in to the eye, in some cases this procedure is itself associated with complications, such as posterior capsule opacification (PCO) requiring further treatment.

The molecular basis of retinal ganglion cell (RGC) development, ageing and death:

We are currently studying apoptosis signalling in the development, degeneration and death of RGCs in the retina.  We are investigating the expression and function of inhibitors of apoptosis (IAPs): Birc2/IAP1, Birc3/Iap2, Birc4/Xiap, Birc5/Survivin, Birc6/Bruce and Birc7/livin and caspases in RGC death during development. The results have implications for greater understanding of the role of these factors in retinal development, ageing and diseases. Furthermore, the retina is a particularly accessible part of the nervous system in which to gain insights into the underlying mechanisms of neurodegenerative diseases including glaucoma. Glaucoma is a complex disease causing visual field loss due to degeneration and death of retinal ganglion cells (RGCs) and characteristic optic neuropathy.

Age related macula degeneration (AMD):

AMD causes damage to the macula, a small spot near the center of the retina and the part of the eye needed for sharp, central vision, which lets us see objects that are straight ahead. In collaboration with Mr David keegan of The Mater Hospital, Dublin we are using microRNA profiling to identify biomarkers in the blood of AMD patients.

 

 

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Last updated: Jun 09 2015.

Last updated 9 June 2015 by SHASSETT@tcd.ie.