Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Kisiswa, Lilian
Languages: English
Types: Doctoral thesis
Subjects: RE
Neuronal viability and connectivity is essential for neuronal function in heath and disease. The aim of this study was to elucidate factors and mechanisms that govern the maintenance and remodelling of RGC dendrites, as well as neuronal cell death in ageing and neurodegenerative diseases. Using PCR technique, the expression pattern of caspases 3,6-9 and inhibitors of apoptosis (lAPs), namely neuronal IAP (NIAP), cellular IAP1 and 2 (clAP1 and 2), X-chromosome linked IAP (XIAP), Survivin, Bruce and Livin was determined in young adult (6 weeks), mature (24-52 weeks), old (88 weeks) and diseased retinae of Wistar albino and Brown Norway (BN) rats. Caspase expression was not altered during maturation and ageing in both strains. In ageing Wistar, NIAP, clAP2 and XIAP and clAP1 were decreased in 88 compared to 24-52 weeks, while Survivin, Bruce and Livin were slightly increased with age. lAPs expression was generally decreased in mature (24- 52 weeks) BN retinae compared to younger (6 weeks). Furthermore, validation of the expression of these molecules at protein level was carried out using western blotting and immunofluorescence techniques. clAP1 protein levels were downregulated in RGCL of BN rats. Reduction of clAP1 did not alter caspase activity but led to impairment in the survival pathway. Older BN retinae demonstrated compromised RGC morphology, but there was no retinal cell loss. Microbead experimental glaucoma model demonstrated no alteration in caspase expression upon induction of glaucoma. NIAP, clAP2, Survivin and Livin were up-regulated, while Bruce was down-regulated in glaucomatous eyes. clAP1 and XIAP expression remain similar between control and experimental eye. In conclusion, reduction in lAPs, which may lead to impairment in survival pathways might be the underlaying cause of reduction in dendrite complexity. Compromised RGC morphology makes a preparatory platform for neurodegenerative process observed in glaucoma disease where age is a major risk factor.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • WEBER, A. J. & HARMAN, C. D. (2005) Structure-function relations of parasol cells in the normal and glaucomatous primate retina. Invest Ophthalmol Vis Sci, 46,3197-207.
    • WEBER, A. J., KAUFMAN, P. L. & HUBBARD, W. C. (1998) Morphology of single ganglion cells in the glaucomatous primate retina. Invest Ophthalmol Vis Sci, 39,2304-20.
    • WEINREB, R. N. & LINDSEY, J. D. (2005) The importance of models in glaucoma research. J Glaucoma, 14,302-4.
    • WEISSE, I. (1995) Changes in the aging rat retina. Ophthalmic Res, 27 Suppl 1, 154-63.
    • WENK, G. L. (2003) Neuropathologic changes in Alzheimer's disease. J Clin Psychiatry, 64 Suppl 9,7-10.
    • WHITMORE, A. V., LIBBY, R. T. & JOHN, S. W. (2005) Glaucoma: thinking in new ways-a role for autonomous axonal self-destruction and other compartmentalised processes? Prog Retin Eye Res, 24, 639-62.
    • WILLIAMS, D. W., KONDO, S., KRZYZANOWSKA, A., HIROMI, Y. & TRUMAN, J. W. (2006) Local caspase activity directs engulfment of dendrites during pruning. Nat Neurosci, 9,1234-6.
    • WOLSZON, L. R., REHDER, V., KATER, S. B. & MACAGNO, E. R. (1994) Calcium wave fronts that cross gap junctions may signal neuronal death during development. J Neurosci, 14,3437-48.
    • WONG, R. O. & GHOSH, A. (2002) Activity-dependent regulation of dendritic growth and patterning. Nat Rev Neurosci, 3, 803-12.
    • WONG, T. P., CAMPBELL, P. M., RIBEIRO-DA-SILVA, A. & CUELLO, A. C. (1998) Synaptic numbers across cortical laminae and cognitive performance of the rat during ageing. Neuroscience, 84,403-12.
    • WRIDE, M. A. (2000) Minireview: apoptosis as seen through a lens. Apoptosis, 5,203-9.
    • WRIDE, M. A., GEATRELL, J. & GUGGENHEIM, J. A. (2006) Proteases in eye development and disease. Birth Defects Res C Embryo Today, 78, 90- 105.
    • WRIDE, M. A., PARKER, E. & SANDERS, E. J. (1999) Members of the bcl-2 and caspase families regulate nuclear degeneration during chick lens fibre differentiation. Dev Biol, 213,142-56.
    • WU, G. Y., DEISSEROTH, K. & TSIEN, R. W. (2001) Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat Neurosci, 4,151-8.
    • WU, R. L., CHEN, T. T. & SUN, T. T. (1994) Functional importance of an Spland an NFkB-related nuclear protein in a keratinocyte-specific promoter of rabbit K3 keratin gene. J Biol Chem, 269,28450-9.
    • XU, H. P., CHEN, H., DING, Q., XIE, Z. H., CHEN, L., DIAO, L., WANG, P., GAN, L., CRAIR, M. C. & TIAN, N. The immune protein CD3zeta is required for normal development of neural circuits in the retina. Neuron, 65,503-15.
    • ZAJA-MILATOVIC, S., MILATOVIC, D., SCHANTZ, A. M., ZHANG, J., MONTINE, K. S., SAMII, A., DEUTCH, A. Y. & MONTINE, T. J. (2005) Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease. Neurology, 64,545-7.
    • ZARNEGAR, B. J., WANG, Y., MAHONEY, D. J., DEMPSEY, P. W., CHEUNG, H. H., HE, J., SHIBA, T., YANG, X., YEH, W. C., MAK, T. W., KORNELUK, R. G. & CHENG, G. (2008) Noncanonical NFkappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAPl, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol, 9,1371-8.
    • 1. Age-related dendrite pruning in the adult Brown Norway (BN) rat retina.
    • Association for Research in Vision and Ophthalmology's (ARVO) 2010 Annual Meeting. Fort Lauderdale, USA.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article