Morphological and functional changes in experimental ocular hypertension and role of neuroprotective drugs.
Glaucoma is a neurodegenerative disease characterized by progressive loss of retinal ganglion cell axons and their cell bodies in the retina. Elevated intraocular pressure (IOP) is considered to be the major risk factor associated with the development of this neuropathy. Randomized controlled clinical trials have demonstrated that in some patients the disease progresses, even after lowering the IOP. Several researchers have devised ways to induce elevated IOP in the rat eye with the aim of impeding the flow of aqueous humour out of the eye. Chronic ocular hypertension in rats induces morphofunctional changes in the optic nerve head and retina. Death of ganglion cells is thought to follow an apoptotic pathway. Changes have also been reported in neuronal and non-neuronal cells, levels of cyclooxygenase, and nitric oxide synthase, endothelin 1 and brain derived neurotrophic factor. Other mechanisms include intracellular electrolyte imbalance, microglial phagocytosis and elevated glutamate levels. Neuroprotection is the treatment strategy by preventing neuronal death. Hypotensive drugs (beta-blockers, alpha-agonists and prostaglandins), Ca++ channel blockers, NMDA antagonists and nitric oxide synthase inhibitors have been used as neuroprotective drugs in experimental models of glaucoma.
García-Campos
J
J
Department of Ophthalmology, School of Medicine, University of Málaga, Málaga, Spain.
Villena
A
A
Díaz
F
F
Vidal
L
L
Moreno
M
M
Pérez de Vargas
I
I
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D010587:Phagocytosis; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D005971:Glutamates; D018696:Neuroprotective Agents; D011453:Prostaglandins; D019001:Nitric Oxide Synthase