The human macula is essential for high acuity vision but its biochemical and cellular properties are poorly understood. A disease that specifically affects the macula, Macular Telangiectasia (MacTel) type2 was investigated by studying postmortem tissue from a single donor. This revealed Müller cell loss specifically in the macula, which might be responsible for the vascular changes and photoreceptor degeneration typical of this disease. To establish whether the disease has subclinical vascular changes outside the macula, the peripheral retina was studied. This showed that contrary to previous reports, abnormal looking capillaries are not disease-specific but a normal ageing phenotype in humans. Proteomics and immunohistochemistry was used to characterise maculae in healthy donors. Comparative proteomics identified differentially expressed proteins and immunohistochemistry confirmed the distribution of selected proteins. This led to the discovery of several Müller cell markers, lactate dehydrogenase (LDHB), glial fibrillary acidic protein (GFAP),αB crystallin (CRYAB) and αA crystallin (CRYAA), which are expressed at higher levels in the macula, demonstrating that Müller cells can take on different differentiation phenotypes depending on retinal area. Furthermore, the spatial expression pattern of LDHB, GFAP and CRYAB was found to correlate with the size/shape of the area that is affected in MacTel type2, providing a possible explanation why the disease affects only the macula. Embryonic development of the macula was investigated in eye tissue obtained from abortions by using immunohistochemistry and gene expression analysis (qPCR and differential gene display). Müller cell markers, CRYAA, CD44 and CRALBP were found to be specifically expressed in the presumptive macula, starting at 7 gestation weeks (CS20), prior to ganglion cell and photoreceptor differentiation. Genomic comparison between this region and peripheral retina revealed further differentially expressed genes and led to the identification of a morphogen, Retinoic acid, which might play a role in macula development in the human retina.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:625837 |
| Date | January 2012 |
| Creators | Powner, M. B. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1348546/ |
Page generated in 0.0023 seconds