[Vaccine for glaucoma, myth or reality?].
The cellular mechanisms involved in the loss of ganglion cells observed in glaucomatous neuropathy are based on a phenomenon of apoptosis: a primary apoptosis, related to the initial hypertonic process whatever its mechanism, and a secondary apoptosis via the free oxygen radicals or nitrogen monoxide, responsible for neuronal degeneration even after the initial factor has disappeared. In addition, glaucoma appears to be characterized by an increase in both TNF-alpha of the glia in the optic-nerve head and its type 1 receptor in the ganglion cells of the retina, which makes them particularly easy to stimulate by TNF-alpha. T lymphocytes also provide a certain neuroprotection by freeing neurotrophins or growth factors when neuronal lesion occurs, according to a specific and active process involving antigen-presenting cells. The T lymphocyte response was stimulated by sensitizing them by epitopes sequestered in the nervous system, notably myelinic proteins, in animal models of ganglion degeneration (obtained via a secondary apoptosis similar to that found during glaucoma). Prevention of ganglion cells loss was also observed by prior immunization of animals using a synthetic polymer close to myelin (COP1), capable of stimulating a specific lymphocyte reaction of neuronal impairment without inducing uveitis. Finally, glial cells, both activated during glaucoma and by TNF-alpha, and secreting TNF-alpha, could serve as antigen-presenting cells and thus constitute the keys to neuroprotection, using an original pathway independent of intraocular pressure control.
Baudouin
C
C
Service d'Ophtalmologie 3, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris. baudouin@quinze-vingts.fr
Liang
H
H
D000818:Animals; D005901:Glaucoma / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007249:Inflammation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014612:Vaccines / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines