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Intravitreal thalidomide reduces experimental preretinal neovascularisation without induction of retinal toxicity
  1. Franziska vom Hagen1,
  2. Bernd A Kamppeter2,
  3. Ralf Erber3,
  4. Jost B Jonas2,
  5. Hans-Peter Hammes1
  1. 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
  2. 2Department of Ophthalmology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
  3. 3Department of Neurosurgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
  1. Correspondence to Prof. Hans-Peter Hammes, 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany; hans-peter.hammes{at}med5.ma.uni-heidelberg.de

Abstract

Background/aims Proliferative retinopathies remain the most common causes of blindness. Retinal neovascularisation is induced by hypoxic upregulation of angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Thalidomide has been shown to be anti-angiogenic via reduction of VEGF levels. We investigated the effect of intravitreal application of thalidomide on neovascularisation and retinal toxicity in a mouse model of proliferative retinopathy.

Methods C57BL/6J mice were exposed to 75% oxygen from postnatal day (p) 7 to p12. Immediately after transfer to room air at p12, mice received an intravitreal injection of 150 μg/μl thalidomide or control solution. Preretinal neovascularisation was quantified at p17. VEGF levels were assessed in whole retinal lysates at p13 and p17. Retinal toxicity was assessed by measuring retinal layer thickness and by analysing caspase-3 activity and apoptotic cell counts in retinal layers to examine retinal apoptosis.

Results Intravitreal application of thalidomide significantly reduced preretinal neovascularisation by 62% compared with control treated contralateral eyes (p=0.01). Interestingly, this effect was established without a change in retinal VEGF levels. Intravitreal thalidomide was not toxic, as retinal layer thickness, retinal caspase-3 activity and apoptotic cell counts were unaltered.

Conclusion These data indicate that intravitreal application of thalidomide can be an effective and safe way to treat retinal neovascularisation.

  • Angiogenesis, apoptosis
  • intravitreal
  • proliferative retinopathy
  • thalidomide

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Footnotes

  • Funding This study was supported by grants from the Deutsche Forschungsgemeinschaft (GRK 880 ‘Vascular Medicine’ for Franziska vom Hagen).

  • Competing interests None declared.

  • Ethics approval All experiments were performed according to the guidelines of the statement of animal experimentation issued by the Association for Research in Vision and Ophthalmology and were approved by the Institutional Animal Care and Use Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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