May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Systemic Neuroprotectin D1 (NPD1) Is a Potent Inhibitor of Laser-Induced Choroidal Neovascularization
Author Affiliations & Notes
  • N. G. Bazan
    Neuroscience and Ophthalmology, LSUHSC, New Orleans, Louisiana
  • Y. Zhou
    Neuroscience and Ophthalmology, LSUHSC, New Orleans, Louisiana
  • J. Elison
    Neuroscience and Ophthalmology, LSUHSC, New Orleans, Louisiana
  • H. Thompson
    Neuroscience and Ophthalmology, LSUHSC, New Orleans, Louisiana
  • P. Gjorstrup
    Resolvyx Pharmaceuticals, Inc., Bedford, Massachusetts
  • W. C. Gordon
    Neuroscience and Ophthalmology, LSUHSC, New Orleans, Louisiana
  • Footnotes
    Commercial Relationships  N.G. Bazan, Resolvyx Pharmaceuticals, Inc., C; Y. Zhou, None; J. Elison, None; H. Thompson, None; P. Gjorstrup, Resolvyx Pharmaceuticals, Inc., I; Resolvyx Pharmaceuticals, Inc., E; W.C. Gordon, None.
  • Footnotes
    Support  Resolvyx Pharmaceuticals, Inc.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5412. doi:https://doi.org/
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    • Get Citation

      N. G. Bazan, Y. Zhou, J. Elison, H. Thompson, P. Gjorstrup, W. C. Gordon; Systemic Neuroprotectin D1 (NPD1) Is a Potent Inhibitor of Laser-Induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5412. doi: https://doi.org/.

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

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Abstract

Purpose: : CNV is the main cause of severe vision loss in the wet form of age-related macular degeneration. We have tested the hypothesis that NPD1, a modulator of pro-inflammatory gene expression and cell survival (N. Bazan, IOVS, 48:4866, 2007), may suppress CNV. For this purpose, we used a CNV model where potential technical artifacts, such as retinal neovascularization and nonspecific local inflammatory activity resulting from the laser injury, are well defined and controlled, to minimize any biased assessment of CNV outcomes.

Methods: : Anesthetized mouse eyes were dilated and 4 lesions were made at 3, 6, 9, and 12 o’clock, around the optic nerve. Pulses were delivered by a green diode Lumenis Novus-Spectra ophthalmic laser mounted on a Topcon slit lamp (SL-D7) (50 µm diameter lesions, 200 mW of energy, and 100 mS duration), and produced a retinal bubble as Bruch’s membrane was breached.NPD1 or vehicle (saline/ethanol) were delivered IP (50 nM stock; 19.0 µg/kg) on days 1, 2, 4, 6, and 8. At days 7 and 14, images of FITC leakage were obtained from each lesion 5 min after IP delivery of FITC. These images were captured and viewed with the Topcon IMAGEnet 2000 LITE digital imaging system, and then ranked as strong, moderate, slight, and none by an ophthalmologist. Strong is equivalent to clinically relevant leakage in humans. Eyes were collected 1 day later and fixed, and retinas removed, leaving a flat-mounted choroid which was labeled with FITC-conjugated Isolectin B4 (specific for endothelial cells). Diameters of choroidal lesions (laser + 15 days) were then plotted to determine the degree of neovascularization.

Results: : Leakage was determined at 7 and 14 days after CNV because at those times, clearly there are no changes of an unspecific nature in inflammatory mediators assessed by LC-MS/MS. By day 7, NPD1 led to reduced leakage to 13% compared to 75% in controls, and by day 14, leakage had been further reduced to 5%, or a protection level of about 90%. Moreover, "none" leakage sites had increased to 68% (15% in controls) by day 14. Choroidal lesion diameters of control retinas increased to about 105 µm, but lesion sites upon NPD1 treatment decreased from 50 µm to about 18 µm at day 14.

Conclusions: : Rapid reduction in leakage from the lesion sites within the first week suggests that systemic NPD1 protects by acting on pathophysiological events during the development of choroidal neovascularization. This is supported by the rapid reduction in lesion site diameter. Thus, NPD1 or analogs of this stereospecific mediator may be of possible therapeutic value for AMD.

Keywords: age-related macular degeneration • choroid: neovascularization • neovascularization 
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