Ординатура / Офтальмология / Английские материалы / Ocular Neuroprotection_Levin, Polo _2003
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Figure 7 (A) IOP time course of cynomolgus monkeys during first DEX treatment. Eleven monkeys were treated with topical glucocorticoid (10 L of 0.1% DEX) three times a day for 28 days. IOP measurements were recorded every 3 to 4 days during 4 weeks of glucocorticoid treatment and for an additional 2 weeks. An elevation of IOP in excess of 5 mmHg was observed in five monkeys that were considered steroid responders. (B) IOP time course during the second DEX treatment. After a 6-month washout period, 10 of the 11 monkeys were re-treated with the same regimen of DEX. Elevated IOP was observed in the same monkeys that had steroid-induced elevations in IOP during the first course of glucocorticoids. Filled circle—IOP of steroid responders at each time point; open circles—IOP of the nonresponding monkeys. Data are mean SD. (From Ref. 147.)
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flow facility by 40–50% for 1–2 months following exchange of the anterior chamber with microgel solution [152]. This was due to accumulation of microgels in the cribriform meshwork and beneath the inner wall of Schlemm’s canal with no cellular alterations or inflammatory infiltrate.
Repeated intracameral injections of 50–100 L of sterile 10 m latex microspheres has recently been used to maintain elevated IOP by TM obstruction for up to 3 years in rhesus monkeys (Fig. 8) [153]. This has the advantage of producing gradual, chronic elevations of IOP without the need for expensive
Figure 8 Histological analysis showing the initial localization of beads injected into the anterior chamber to the region of the TM (top) and their intense packing density following multiple injections (bottom). Beads distributed to the iris had no adverse effect on its function. (From Ref. 153.)
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ophthalmic equipment, without producing inflammation, and without compromising visibility of the optic disc.
5. Enzymes
Injection of alpha chymotrypsin into the posterior chamber rapidly increases IOP and is also accompanied by iridocyclitis, lens displacement, ciliary body atrophy, anterior chamber angle deformation, and peripheral anterior synechiae [154– 156]. IOP elevation can persist for at least 6 months or longer.
III. CONCLUDING REMARKS
Laser-induced ocular hypertension is currently the most commonly used and most extensively characterized model for experimental glaucoma in primates. It mimics the optic neuropathy affecting the entire visual pathway, analogous to the human disease, and also amplifies the IOP-lowering effect of drugs. It has thus provided, and will no doubt continue to provide, useful pathophysiological and therapeutic insights relevant to the human disease. Other promising primate models including bead injections and steroid administration await more comprehensive characterization to enhance our understanding of the situations in which they will be most useful.
ACKNOWLEDGMENTS
We thank Drs. Jay McLaren and Richard Brubaker for their contributions to the aqueous humor formation section and Dr. T. Michael Nork for his contribution to the photoreceptor section.
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