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Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma.
Invest Ophthalmol Vis Sci. 2002 Sep; 43(9):2962-8.IO

Abstract

PURPOSE

To characterize the early reaction of retinal ganglion cells (RGCs) in a rat model of glaucoma using in vivo imaging and to examine the involvement of retinal microglia in glaucomatous neuropathy.

METHODS

Glaucoma was induced in adult female Sprague-Dawley rats by cauterizing two episcleral veins, which resulted in a 1.6-fold increase in intraocular pressure (IOP). Retinal ganglion cells were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]-N-methyl-pyridinium-iodide (4-Di-10ASP) and monitored in vivo after elevation of IOP using fluorescence microscopy imaging. The number of RGCs was quantified on retinal flatmounts. Dying RGCs were surrounded by activated microglia that became visible after taking up the fluorescent debris. Immunocytochemistry was conducted to characterize further the ganglion cells and microglia.

RESULTS

Cauterizing two of the four episcleral veins resulted in a consistent increase of IOP to 25.3 +/- 2.0 mm Hg, as measured with a handheld tonometer. IOP remained high for at least 3 months in glaucomatous eyes. The earliest sign of RGC death was detected in anesthetized animals 20 hours after induction of glaucoma. RGCs continued to decrease in number over time, with 40% of RGCs having degenerated after 2.5 months. Fundoscopic examination of the optic nerve head revealed cupping 2 months after induction of glaucoma. In addition, microglia were detected on retinal flatmounts as early as 72 hours after induction. Activated microglia and RGCs were also identified immunocytochemically, with an antibody against ionized calcium-binding adaptor molecule (Iba)-1 and an antibody specific to the 200-kDa subunit of the neurofilament protein, respectively.

CONCLUSIONS

Occlusion of episcleral veins is a reproducible method that mimics human glaucoma, with chronically elevated IOP-induced RGC loss. This study shows that in vivo imaging permits the detection of ganglion cells in the living animal in the early stages of the disease and highlights the importance of in vivo imaging in understanding ophthalmic disorders such as glaucoma. Secondly, activation of intraretinal microglia coincides with degeneration of RGCs in glaucoma.

Authors+Show Affiliations

Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Münster, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12202516

Citation

Naskar, Rita, et al. "Detection of Early Neuron Degeneration and Accompanying Microglial Responses in the Retina of a Rat Model of Glaucoma." Investigative Ophthalmology & Visual Science, vol. 43, no. 9, 2002, pp. 2962-8.
Naskar R, Wissing M, Thanos S. Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. Invest Ophthalmol Vis Sci. 2002;43(9):2962-8.
Naskar, R., Wissing, M., & Thanos, S. (2002). Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. Investigative Ophthalmology & Visual Science, 43(9), 2962-8.
Naskar R, Wissing M, Thanos S. Detection of Early Neuron Degeneration and Accompanying Microglial Responses in the Retina of a Rat Model of Glaucoma. Invest Ophthalmol Vis Sci. 2002;43(9):2962-8. PubMed PMID: 12202516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. AU - Naskar,Rita, AU - Wissing,Mechthild, AU - Thanos,Solon, PY - 2002/8/31/pubmed PY - 2002/9/13/medline PY - 2002/8/31/entrez SP - 2962 EP - 8 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 43 IS - 9 N2 - PURPOSE: To characterize the early reaction of retinal ganglion cells (RGCs) in a rat model of glaucoma using in vivo imaging and to examine the involvement of retinal microglia in glaucomatous neuropathy. METHODS: Glaucoma was induced in adult female Sprague-Dawley rats by cauterizing two episcleral veins, which resulted in a 1.6-fold increase in intraocular pressure (IOP). Retinal ganglion cells were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]-N-methyl-pyridinium-iodide (4-Di-10ASP) and monitored in vivo after elevation of IOP using fluorescence microscopy imaging. The number of RGCs was quantified on retinal flatmounts. Dying RGCs were surrounded by activated microglia that became visible after taking up the fluorescent debris. Immunocytochemistry was conducted to characterize further the ganglion cells and microglia. RESULTS: Cauterizing two of the four episcleral veins resulted in a consistent increase of IOP to 25.3 +/- 2.0 mm Hg, as measured with a handheld tonometer. IOP remained high for at least 3 months in glaucomatous eyes. The earliest sign of RGC death was detected in anesthetized animals 20 hours after induction of glaucoma. RGCs continued to decrease in number over time, with 40% of RGCs having degenerated after 2.5 months. Fundoscopic examination of the optic nerve head revealed cupping 2 months after induction of glaucoma. In addition, microglia were detected on retinal flatmounts as early as 72 hours after induction. Activated microglia and RGCs were also identified immunocytochemically, with an antibody against ionized calcium-binding adaptor molecule (Iba)-1 and an antibody specific to the 200-kDa subunit of the neurofilament protein, respectively. CONCLUSIONS: Occlusion of episcleral veins is a reproducible method that mimics human glaucoma, with chronically elevated IOP-induced RGC loss. This study shows that in vivo imaging permits the detection of ganglion cells in the living animal in the early stages of the disease and highlights the importance of in vivo imaging in understanding ophthalmic disorders such as glaucoma. Secondly, activation of intraretinal microglia coincides with degeneration of RGCs in glaucoma. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/12202516/Detection_of_early_neuron_degeneration_and_accompanying_microglial_responses_in_the_retina_of_a_rat_model_of_glaucoma_ L2 - https://iovs.arvojournals.org/article.aspx?volume=43&issue=9&page=2962 DB - PRIME DP - Unbound Medicine ER -