Details

Autor(en) / Beteiligte

• Lin, Yanhua
• Jones, Bryan W.
• Liu, Aihua
• Tucker, James F.
• Rapp, Kevin
• Luo, Ling
• Baehr, Wolfgang
• Bernstein, Paul S.
• Watt, Carl B.
• Yang, Jia‐Hui
• Shaw, Marguerite V.
• Marc, Robert E.

Titel

Retinoid receptors trigger neuritogenesis in retinal degenerations

Ist Teil von

• The FASEB journal, 2012-01, Vol.26 (1), p.81-92

Ort / Verlag

United States: Federation of American Societies for Experimental Biology

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• ABSTRACT Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented retina and brain regions. Using the light‐induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron neuritogenesis and up‐regulated several key elements of retinoic acid (RA) signaling, including retinoid X receptors (RXRs). Exogenous RA initiated neuritogenesis in normal adult retinas and primary retinal cultures and exacerbated it in LIRD retinas. However, LIRD‐induced neuritogenesis was partly attenuated in retinol dehydrogenase knockout (Rdh12−/−) mice and by aldehyde dehydrogenase inhibitors. We further found that LIRD rapidly increased the expression of glutamate receptor 2 and β Ca2+/ calmodulin‐dependent protein kinase II (pCaMKII). Pulldown assays demonstrated interaction between PCaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR antagonists completely prevented and RXR agonists were more effective than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and may be therapeutic targets to attenuate retinal remodeling and facilitate global intervention methods in blinding diseases and other neurodegenerative disorders.—Lin, Y., Jones, B. W., Liu, A., Tucker, J. F., Rapp, K., Luo, L., Baehr, W., Bernstein, P. S., Watt, C. B., Yang, J.‐H., Shaw, M. V., Marc, R. E. Retinoid receptors trigger neuritogenesis in retinal degenerations. FASEB J. 26, 81–92 (2012). www.fasebj.org