May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Novel Endocannabinoids Confer Neuroprotection in NMDA Rat Model
Author Affiliations & Notes
  • S.S. Samudre
    TR Lee Ctr. for Ocular Pharm., Estrn Va Med School, Norfolk, VA
  • P.B. Williams
    TR Lee Ctr. for Ocular Pharm., Estrn Va Med School, Norfolk, VA
  • B.R. Martin
    Pharmacology and Toxicology, Va Cmmwlth Univ–Med Coll of Va, Richmond, VA
  • I.G. Castillo
    Pharmacology and Toxicology, Va Cmmwlth Univ–Med Coll of Va, Richmond, VA
  • A. Hosseini
    TR Lee Ctr. for Ocular Pharm., Estrn Va Med School, Norfolk, VA
  • F.A. Lattanzio, Jr.
    TR Lee Ctr. for Ocular Pharm., Estrn Va Med School, Norfolk, VA
  • Footnotes
    Commercial Relationships  S.S. Samudre, None; P.B. Williams, None; B.R. Martin, None; I.G. Castillo, None; A. Hosseini, None; F.A. Lattanzio, None.
  • Footnotes
    Support  Richmond Eye and Ear Foundation
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1566. doi:
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      S.S. Samudre, P.B. Williams, B.R. Martin, I.G. Castillo, A. Hosseini, F.A. Lattanzio, Jr.; Novel Endocannabinoids Confer Neuroprotection in NMDA Rat Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1566.

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

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Abstract
 
Purpose:
 

Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of endogenous cannabinoid analogs decreases IOP in a rat model of glaucoma. Based upon their effects on other tissues, we hypothesize that these analogs may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if these novel CB agonists, lipid soluble O–1812 (CB1> 2), and water soluble O–2545 (CB 1, 2) confer retinal neuroprotection.

 
Methods:
 

Retinal damage was induced by intravitreal injection of NMDA (2 µl of 10 mM) in Sprague–Dawley rats. In other groups 2 µl O–1812 (2 mM) or 2 µl O–2545 (2mM) were co–injected with NMDA. Electroretinograms (ERG) were recorded at baseline, 1 wk and 2 wk after injection. Contralateral normal eyes served as controls. After 2 wk, retinas were flat mounted and stained with H&E. In other experiments, IOP was obtained following topically applied O–1812 or O–2545.

 
Results:
 

At 1 wk, a–wave amplitude in all treatments was depressed with no functional change in b–wave. O–1812 was most effective in restricting functional loss of a–wave amplitude. At 2 wk, a–wave amplitudes improved only in drug treated group. O–1812 most effectively restored a–wave amplitude towards baseline; O–2545 was less effective. The a–wave amplitude in NMDA treated group continued to decline with the damage extending to b–wave amplitude. Both drugs significantly reduced IOP by 79 % 30 min after O–1812; by 78 % 60 min after O–2545 (p<0.05). Retinal whole mounts after NMDA alone showed areas devoid of cells, while those treated with O–1812 and O–2545 were intact with an even distribution of retinal ganglionic cells.  

 
Conclusions:
 

Both compounds partially preserved functional a–waves, completely prevented b–wave loss, and maintained a normal distribution of ganglionic cells. Considering both IOP and neuroprotective effects, lipid soluble O–1812 was most effective.

 
Keywords: electroretinography: non-clinical • neuroprotection • drug toxicity/drug effects 
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