September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The DRUGSFORD project: Preservation of retinal morphology and function in different in vivo models for hereditary retinal degeneration
Author Affiliations & Notes
  • Francois Paquet-Durand
    Institute for Ophthalmic Research, Tuebingen, Germany
  • Dragana Trifunovic
    Institute for Ophthalmic Research, Tuebingen, Germany
  • Ayse Sahaboglu
    Institute for Ophthalmic Research, Tuebingen, Germany
  • Tobias Peters
    Institute for Ophthalmic Research, Tuebingen, Germany
  • Torsten Strasser
    Institute for Ophthalmic Research, Tuebingen, Germany
  • Patricia Veiga-Crespo
    Lund University, Lund, Sweden
  • Hans-Gottfried Genieser
    Biolog Life Science Institute, Bremen, Germany
  • Pieter Gaillard
    2-BBB Medicines BV, Leiden, Netherlands
  • Valeria Marigo
    University of Modena and Reggio Emilia, Modena, Italy
  • Per A R Ekström
    Lund University, Lund, Sweden
  • Footnotes
    Commercial Relationships   Francois Paquet-Durand, None; Dragana Trifunovic, None; Ayse Sahaboglu, None; Tobias Peters, None; Torsten Strasser, None; Patricia Veiga-Crespo, None; Hans-Gottfried Genieser, Biolog (E); Pieter Gaillard, 2-BBB (E); Valeria Marigo, None; Per Ekström, None
  • Footnotes
    Support  European Union (HEALTH-F2-2012-304963)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4394. doi:
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      Francois Paquet-Durand, Dragana Trifunovic, Ayse Sahaboglu, Tobias Peters, Torsten Strasser, Patricia Veiga-Crespo, Hans-Gottfried Genieser, Pieter Gaillard, Valeria Marigo, Per A R Ekström; The DRUGSFORD project: Preservation of retinal morphology and function in different in vivo models for hereditary retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4394.

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

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Purpose : Hereditary retinal degeneration (RD) relates to a genetically heterogeneous group of diseases leading to photoreceptor degeneration and blindness. In many RD subtypes an excessive accumulation of cGMP in photoreceptors has been observed, providing a common target for photoreceptor protection. The DRUGSFORD project aims at generating new compounds combined with a drug delivery system (DDS), to selectively rebalance cGMP-signalling. Here, we report about the project's first lead compound formulation - LP-DF003 - showing photoreceptor protective properties in several in vivo RD models.

Methods : To identify the best application paradigm for compound and DDS combinations, topical, intravitreal, subtenonal, intraperitoneal, and intravenous applications were tested using fluorescent DDS and scanning laser ophthalmoscopy. The treatment effect was then tested in vivo on rd1, rd2, and rd10 mice using intraperitoneal injections, the effects were analysed using electroretinography and histology.

Results : In rapidly degenerating rd1 mice, LP-DF003 treatment significantly slowed down the degenerative process resulting in 29% (±8.1 SEM, n=8, p<0.01) more surviving photoreceptors at post-natal day (P) 14. In the more slowly degenerating rd2 and rd10 animals, at P30, photoreceptor survival was improved by 11% (±2.9, n=8, p<0.05) and 27% (±11, n=12, p<0.05), respectively. Importantly, P30 ERG recordings in rd2 and rd10 animals showed significantly increased light responses (average b-wave amplitudes at 3.0 cd.s/m2, rd2: +46% ±15.2 SEM, n=7, p<0.01; rd10: +332% ±142, n=8, p<0.001).

Conclusions : We show that LP-DF003 increases photoreceptor viability in three different in vivo RD models, with robust improvement of retinal function in two RD models. The rd2 and rd10 animals carry mutations in two different genes (Prph2 and Pde6b, respectively), suggesting a general applicability of LP-DF003 treatment to a variety of different RD subtypes with significant promise for future clinical development.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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