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W. Shen, S. Li, M. C. Gillies; Selective Disturbance of MüLler Cell Function Leads to Retinal Vascular Changes in Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3973. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal Müller cells span the entire thickness of the tissue and ensheath all retinal neurons. Reactive Müller cell gliosis is associated with every type of retinal diseases but the relationship between Müller cell dysfunction and retinal vascular changes remains unclear. This study aimed to investigate changes in the retinal vasculature after selective disturbance of Müller cells in normal and RCS rats.
DL- and L-α-aminoadipic acid (α-AAA), two isoforms of a glia-specific toxin, were injected intravitreally or subretinally with doses ranging from 16 to 100 µg/eye in normal and RCS rats. The injected animals were monitored by fluorescein angiography for retinal vascular changes between 2 days and 2 months post injection. Retinal vascular changes revealed by angiography were further examined by confocal microscopy using retinal wholemounts after perfusion with fluorescence conjugated dextran (MW=2.0 x106). To map retinal vascular changes with Müller cell disturbance, lectin B4 histochemistry and expression of vimentin, a biomarker for Müller cells, were examined after α-AAA injection.
Both intravitreal and subretinal injections of α-AAA induced both dose- and isoform-dependent retinal vascular leakage and telangiectasia from one week post injection, with the most effective changes in eyes receiving 100 µg of L-α-AAA. Confocal microscopy revealed changes in super-facial and deep retinal vascular beds. Retinal vascular changes seemed to be reversible in eyes receiving 16 µg of DL-α-AAA. Double staining for lectin B4 and vimentin demonstrated that vascular changes occurred predominantly in the region where Müller cells were disturbed. Interestingly, retinal vascular changes in RCS rats were further enhanced by α-AAA-induced Müller cell disturbance.
Müller cell dysfunction induced by α-AAA leads to retinal vascular leakage and telangiectasia. This observation may have clinical significance in explaining the role of Müller cells in several retinal diseases such as diabetic retinopathy, idiopathic perimacular telangiectasia, age-related macular degeneration and other forms of retinal degenerations.
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