Elsevier

Neuroscience

Volume 139, Issue 2, 2006, Pages 723-732
Neuroscience

Sensory system
Müller glial cells express nestin coupled with glial fibrillary acidic protein in experimentally induced glaucoma in the rat retina

https://doi.org/10.1016/j.neuroscience.2005.12.032Get rights and content

Abstract

This study was aimed to investigate reactive changes of Müller glial cells in rats subjected to experimentally induced glaucoma. In the latter, it is well documented that elevated intraocular pressure leads to the loss of ganglion cells as confirmed in this study. The present results have shown that Müller glial cells as well as astrocytes closely associated with the ganglion cells reacted vigorously to increased intraocular pressure as manifested by the induced and upregulated expression of nestin and glial fibrillar acidic protein. A major finding in glaucomatous rats was the induced expression of nestin together with glial fibrillar acidic protein with the rise of the intraocular pressure beginning at 2 h. The marked nestin expression appeared to be most intense at 1 week after operation and was sustained at 3 weeks. Induced nestin expression in Müller glial cells was demonstrated unequivocally in whole-mount preparation of the retina. In the same tissue preparation, nestin expression was also detected in some astrocytes. Western blotting analysis confirmed a marked increase in expression of nestin and glial fibrillar acidic protein. Present results suggest that nestin as well as glial fibrillar acidic protein is a useful biomarker for retina injury. The induced expression of these intermediate filament proteins in Müller glial cells especially at their end-feet and also in some astrocytes adjoining the neuronal injury suggests a potential neuroprotective mechanism in response to acute rise in intraocular pressure resulting in neuronal degeneration.

Section snippets

Experimental procedures

A total of 41 adult female Wistar rats (weighing 180∼240g; aged 8 weeks) were used in this study. Food and water were provided ad libitum, and the animals were maintained on a 12-h light/dark cycle. Two rats were used for normal study, 39 rats for experimental glaucoma induction. In the handling and care of all animals, the International Guiding Principles for animals research, as stipulated by the Council for International Organizations of Medical Science (CIOMS) (1985) and as adopted by the

IOP

In the normal and sham-operated control eyes, the baseline IOP of rats was 17.57±0.42 mm Hg. At 2 h after operation, the mean IOP of the experimental eyes was immediately increased to 26.77±1.68 mm Hg. This was further raised with time, peaking at 1 day to reach 27.10±1.27 mm Hg, that was 1.55-fold over baseline. The significant elevation in IOP was sustained throughout the experimental period (P<0.01) (Fig. 1). The ocular tissues including the cornea, lens and sclera appeared structurally

Discussion

Damage of the inner retinal layers leading to the loss of ganglion cells and their axons in glaucomatous models has been well documented using different conventional histological methods as well as apoptotic markers (Glovinsky et al 1993, Garcia-Valenzuela et al 1995, Wygnanski et al 1995, Laquis et al 1998, Wang et al 2000). The present results corroborate this showing a significant loss of NeuN labeled ganglion cells beginning at 1 week postoperation with the rise of the IOP. Concomitant to

Conclusion

In conclusion, the central goal of this study was to examine the reactive changes of Müller glial cells to glaucoma. It is unequivocal that elevated IOP induces Müller glial cell activation as manifested by an increase in GFAP and nestin expression. The induced expression of nestin along with the increased expression of GFAP in Müller glial cells may reflect a metabolic change of the cells in response to the degenerative changes of their neighboring ganglion cells whose functions are closely

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