December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Diltiazem-Induced Neuroprotection in an In Vitro Model of Photoreceptor Degeneration
Author Affiliations & Notes
  • SA Picaud
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • G Vallazza
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • D Cia
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • A Duboc
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • V Forster
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • L-H Tessier
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • JA Sahel
    Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine INSERM Strasbourg France
  • Footnotes
    Commercial Relationships   S.A. Picaud, None; G. Vallazza, None; D. Cia, None; A. Duboc, None; V. Forster, None; L. Tessier, None; J.A. Sahel, None. Grant Identification: INSERM, Retina-France
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1886. doi:
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      SA Picaud, G Vallazza, D Cia, A Duboc, V Forster, L-H Tessier, JA Sahel; Diltiazem-Induced Neuroprotection in an In Vitro Model of Photoreceptor Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1886.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: We previously reported diltiazem-induced neuroprotection of photoreceptors in the rd mouse retina (Frasson et al., 1999). To further assess the cellular mechanism of this neuroprotection, we adapted on the rat retina an in vitro model of photoreceptor degeneration developed by Ulshafer et al. (1980). Furthermore, to correlate the diltiazem-induced neuroprotection of photoreceptors and its effect on Ca2+ channels, we measured the diltiazem inhibition on Ca2+ currents in isolated rod photoreceptors. Methods: Retinal explants of adult rats were prepared on polycarbonate membrane following papain treatment of isolated eyes. Retinae were then incubated in the presence or absence of the phosphodiesterase inhibitor, zaprinast. Retinal explants were fixed in paraformaldehyde and photoreceptor cell death was assessed on sections. For their patch clamp recording, rod photoreceptors were isolated from the pig retina and dissociated with a papain treatment and mechanical dissociation. Results: When treated with zaprinast, 20% of photoreceptors underwent cell death as indicated by TUNEL labelling whereas only 2.2% of photoreceptors were labelled in control explants. In the presence of diltiazem in addition to zaprinast, the number of TUNEL-positive photoreceptors was reduced to 8,4%. Diltiazem by itself increased the number of TUNEL-positive photoreceptors to 5.9%. In rod photoreceptors, Ca2+ currents were activated at -60mV and were maximum around -20mV when measured in the presence of 5mM extracellular Ca2+; 5mM Cs+ and 30mM tetraethylamonium (TEA) were added to the medium to suppress K+ currents. Under these conditions, diltiazem (100µM)decreased by 54% the Ca2+ currents measured by Cd2+ (100µM) inhibition. Conclusion: These results are consistent with diltiazem neuroprotection of photoreceptors. They suggest further that an excess of intracellular cGMP can trigger photoreceptor degeneration as a consequence of altered Ca2+ influx.

Keywords: 517 photoreceptors • 514 pharmacology • 489 neuroprotection 
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