Protective effect of retinal ischemia by blockers of voltage-dependent calcium channels and intracellular calcium stores.
In the present study, the neuroprotective effect of blockers of voltage-dependent calcium channels (VDCC) and intracellular calcium stores on retinal ischemic damage induced by oxygen deprivation-low glucose insult (ODLG) was investigated. Retinal damage induced by ODLG was dependent on the calcium concentration in the perfusion medium. When incubated in medium containing 2.4 mM CaCl(2), cell death in ischemic retinal slices treated with blockers of VDCC, omega-conotoxin GVIA (1.0 microM), omega-conotoxin MVIIC (100 nM) and nifedipine (1.0 microM), was reduced to 62 +/- 2.3, 46 +/- 4.3 and 47 +/- 3.9%, respectively. In the presence of blockers of intracellular calcium stores, dantrolene (100 microM) and 2-APB (100 microM), the cell death was reduced to 46 +/- 3.2 and 55 +/- 2.9%, respectively. Tetrodotoxin (1.0 microM), reducing the extent of the membrane depolarization reduces the magnitude of calcium influx trough VDCC causing a reduction of the cell death to 55 +/- 4.3. Lactate dehydrogenase content of untreated ischemic retinal slices was reduced by 37% and treatment of ischemic slices with BAPTA-AM (100 microM) or 2-APB (100 microM) abolished the leakage of LDH. Dantrolene (100 microM) and nifedipine (1.0 microM) partially blocked the induced reduction on the LDH content of retinal ischemic slices. Histological analysis of retinal ischemic slices showed 40% reduction of ganglion cells that was prevented by BAPTA-AM or dantrolene. 2-APB partially blocked this reduction whilst nifedipine had no effect, p > 0.95. Conclusion Blockers of VDCC and intracellular calcium-sensitive receptors exert neuroprotective effect on retinal ischemia.
Massote
Pindaro Dias
PD
Nucleo Pós Graduação Santa Casa, Belo Horizonte, MG, Brazil.
Pinheiro
Ana Cristina Nascimento
AC
Fonseca
Cristina Guatimosim
CG
Prado
Marco Antonio Máximo
MA
Guimarães
André L S
AL
Massensini
André R
AR
Gomez
Marcus Vinicius
MV
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018613:Microscopy, Confocal; D010100:Oxygen / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D005947:Glucose; D010100:Oxygen; D002118:Calcium