The Research for Elucidation of Molecular Mechanism of Glaucomatous Optic Neuropathy and Development of Efficacious Treatment

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Visco-elastic solution Healon-V* was intra-camerally injected in the unilateral eye of two cynomolgus monkeys, and experimental acute glaucoma model eyes were produced. The intraocular pressure (IOP) was measured by Parkins' applanation tonometer, and the IOP of the two glaucomatous eyes were confirmed to be sustained over 30mmHg, while those of contralateral control eyes were under 15mmHg. After the IOP elevation of 3 days, the monkeys were painlessly sacrificed, and the glaucomatous and control eyes were enucleated including retrobulbar optic nerve. The lamina cribrosa tissue including pre-laminar and post-laminar portion were excised under binocular microscope, and the total RNA was extracted and purified. DNA microarray, Human Genome U133 2.0 Array, Affimetrix (Oligo-array, single color, approximately 39,000 transcriptional products) were utilized to detect up/down regulated RNA after IOP elevation, and the data was analyzed with Atlas-Image 2.01. Ninety up-regulated genes were selected under the condition of "detection : present-present" and "signal log ratio > 2.0", and 62 down-regulated genes were selected under the condition of "signal log ratio <-2.0". Up-regulated genes included cytoskeleton (profilin 1, thrombospondin 2, protocadherin 8, CD44 antigen, BMP-2), signal transduction (G protein), extracellular matrix (collagen types IV, VI, XV), immune response (guanylate binding protein 2), transcription factor (v-fos, junB), transport (ceruloplasmin), TIMP-1, etc. Down-regulated genes included cytoskeleton (oligodendrocyte myelin glycoprotein), immune response (myelin basic protein), transcription factor (oligodendrocyte transcription factor 1), TGF-2, etc. Meanwhile, there was no significant increase or decrease in the gene expression related to tissue remodeling in the acute phase of IOP elevation.