Neuroprotection in Glaucoma-

present and future

Roman Goś

Department of Ophthalmology

and Visual Rehabilitation

Łódź



Is it still an IOP-dependent phenomenon?

results of

AGIS study group



Ischemia/ hypoxia



Mechanical trauma



Axoplasmic transport disturbance



Free oxygen radicals



Nitric oxide



glutamates



Changes in ion concentrations



Increased concentrations of free radicals



Neuromediators release



Immunological system activation

Increased activity

of nitric oxide

syntase in

astrocytes



Mitochondria in

nerve fibre



O²ˉ



OHˉ



apoptosis



Activation of NMDA receptor



Cellular Influx of calcium ions



Activation of intracellular enzymes



apoptosis



Pharmacological



Immunological



Schwartz M>Eur.J.Ophthalmol,2003,supp

3,27



Glutamate antagonists



Calcium channel blockers



Antioxidants



NOS Inhibitors



Neurotrophins



Antiapoptotic factors/ kaspase inhibitors



Betaksolol – blocks voltage-dependent

calcium channels ,stimulates syntase of

BDNF



Brimonidine



Memantine



Niphedipine



Citicoline



Ophthalmology,1999,106,1126-1134



Med.Sci.Mon, 2003,9,24-28



Only betaksolol blocks sodium and

calcium channels of RGC



Sponsel W.E et all: Periocular

accumulation of timolol and betaksalol in

glaucoma patients on long-term therapy



Surv.Ophthalmol 1999,43,210=213



Function of immunological system in

glaucoma



Perspectives of immunoneuropeotection



Increased IOP stimulates astrocytes to

express

HLA-

DR gene

Liu .B et

all.

Arch.Ophth,2001,119,240-

245



Glaucomatous eyes contain antibodies

against glikosaminoglicans and

proteoglicans of lamina cribrosa



Immunohistochemical studies confirm

changes in quantity and distribution of

antibodies in glaucomatous eyes.

Tezel G,Arch.Ophth.1999,117,917-

924



In glaucoma there is an increased

antibody antigen ratio for retinal

antigens;rhodopsin,enolase

glicoaminoglicans and glutation

transpherase

Joachim S.C.et all, Graefes Ach Clin

.Exp.Ophth ,2005



Protective role of immune system

activation in CNS damage

Schwartz M.et all

J.Neuroimmnol

2001,113,18-192



Vaccination with spinal cord homogenate

protects RGC after injury

Ellzam B.J.et all.:Neurol.Disease

2003,12,1-10



Vaccination with R-16- peptide from

retinoid binding protein



Immunisation with syntetic copolimer

-Cop 1

Bekalash S. Et

all.Invest.Ophth, 2003,44,3374 Schori H.

Et all. Proc.Nat.Acad.USA, 2001,98,3398



Vaccination for glaucoma :dream or

reality?

Schwartz

M:Brain .Res.Bull.

2004,62,481





Haefliger et all.:

In glaucoma , should

enthusiasm about neuroprotection be

tempered by the experience obtained in

other neurodegerative disorders?

Eye,2000,14,464