POSSIBLE CONSTITUTIONAL RISK FACTORS FOR GLAUCOMA DAMAGE (WITH AN EMPHASIS ON THE INVESTIGATION OF DEFICIENT ENDOGENOUS NEUROPROTECTION)

Joseph Caprioli, MD

1. Putative risk factors for glaucoma (restricted here to those not clearly related to genetics)
1. Sociological
1. Age
2. Gender
3. Occupation
4. Level of education
2. Anthropometric
1. Height/weight index
3. Systemic Medical
1. Hypertension
2. Nocturnal hypotension
3. Diabetes
4. Cardiovascular disease
5. Vasospasm
6. Hypothyroid
7. Helicobacter pylori infection
8. Obesity
4. Ocular
1. Iris color
2. Pseudoexfoliation
3. IOP
4. myopia
5. Dietary
1. Vitamin deficiency
2. Zinc deficiency
3. Caloric excess
6. Habitual
1. Smoking
2. Alcohol consumption
7. Deficient endogenous protection
1. Deficient stress protein response
2. Dysregulation of apoptotic pathways
2. Good evidence FOR the following:
1. Age
2. Gender
3. Vasospasm
4. Nocturnal hypotension
5. Iris color
6. IOP
7. Pseudoexfoliation
3. Good evidence AGAINST the following:
1. Hypothyroid
2. Helicobacter pylori infection
4. Possible risk factors which should be taken into account clinically, can be modified, but as yet remain unproven as causative or associated with glaucoma:
1. Chronic vascular disease caused by hypertension
2. Diabetes
3. Smoking
4. Obesity (low ht/wt index)
5. Deficient endogenous neuroprotection
1. Heat shock protein response (stress response)
2. “That which doesn't kill you, makes you stronger”
3. Variety of stressors promote synthesis of heat shock proteins (HSP) of various families and molecular weight
4. Genetic code for these proteins highly conserved across species, which implies a fundamentally important process.
5. Hyperthermic pre-conditioning protects RGCs from NMDA-induced apoptosis and IOP induced damage in a rat model
1. Mechanisim appears to be induction of HSP72
2. Protective effect blocked by quercetin, a HSP synthesis blocker
6. HSP-inducing drugs: Geranyl-geranyl-acetone (GGA, teprenone)
1. Induces transcriptional activation of HSP72
2. Increases resistance of gastric mucosa to irritants and stress
7. GGA protects RGCs in a rat glaucoma model
1. Protective effect abolished by quercetin
2. HSP72 induced in RGCs by GGA
8. Caloric deprivation and 2-dG also protects RGCs from NMDA and IOP related death
1. Decreased rates of apoptosis
2. Lean and mean may be good!
9. Periodic hyperthermia (sauna or steam bath) and caloric restriction (run a little lean) may be factors that promote endogenous neuroprotection and reduce RGC trauma from IOP and other damaging factors, whatever and how numerous they may be.

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