Scientific Publications

Preclinical Studies of Eyevensys Products in Development

Neuroprotective Effects of Transferrin in Experimental Glaucoma Models

Youale J, Bigot K, Kodati B, Jaworski T, Fan Y, Nsiah NY, Pappenhagen N, Inman DM, Behar-Cohen F, Bordet T, Picard E. Int J Mol Sci. 2022;23(21):12753. Published 2022 Oct 22.

  • Researchers assessed the protective effects of transferrin on retinal ganglion cell (RGC) survival using ex vivo and in vivo rat models
  • In rat retinal explants exposed to iron, NMDA-induced excitotoxicity, or CoCl2-induced hypoxia, transferrin significantly preserved RGCs and protected them from apoptosis, ferroptosis, and necrosis
  • In a rat model of ocular hypertension, transferrin reduced RGC loss by about 70% (vs treatment with vehicle) and preserved about 47% of axons

Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration

Bigot K, Gondouin P, Bénard R, Montagne P, Youale J, Piazza M, Picard E, Bordet T, Behar-Cohen F. Pharmaceutics. 2020;12(9):836. Published 2020 Sep 1.

  • pEYS611 is a plasmid encoding human transferrin, an endogenous iron chelator with therapeutic potential in retinitis pigmentosa (RP) and age-related macular degeneration (AMD)
  • In this study, researchers evaluated the efficacy of pEYS611 in 3 animal models of retinal degeneration induced by photo-oxidation, N-methyl-N-nitrosourea, or genetic predisposition (RCS rat)

Iron is Neurotoxic in Retinal Detachment and Transferrin Confers Neuroprotection

Daruich A, Le Rouzic Q, Jonet L, Naud MC, Kowalczuk L, Pournaras JA, Boatright JH, Thomas A, Turck N, Moulin A, Behar-Cohen F, Picard E. Sci Adv. 2019;5(1):eaau9940. Published 2019 Jan 9.

  • Researchers explored the roles that iron and transferrin play in retinal detachment-induced tissue degeneration
  • Poor visual recovery was associated with elevated iron and transferrin levels in ocular specimens collected from patients with retinal detachment
  • Experiments in animal models found iron accumulation induced cell death, which was mitigated by transferrin

Non-Viral Ocular Gene Therapy, peys606, for the Treatment of Non-Infectious Uveitis: Preclinical Evaluation of the Medicinal Product

Touchard E, Benard R, Bigot K, Laffitte JD, Buggage R, Bordet T, Behar-Cohen F. J Control Release. 2018;285:244-251.

  • Researchers report the development steps of pEYS606, a clinical-grade plasmid DNA that encodes a fusion protein with high affinity for human TNF-α, a therapeutic target for non-infectious uveitis
  • pEYS606 demonstrated significant reductions of ocular inflammation in two established rat models of uveitis (endotoxin-induced uveitis and experimental autoimmune uveitis)

Overexpressed or Intraperitoneally Injected Human Transferrin Prevents Photoreceptor Degeneration in rd10 Mice

Picard E, Jonet L, Sergeant C, Vesvres MH, Behar-Cohen F, Courtois Y, Jeanny JC. Mol Vis. 2010;16:2612-2625. Published 2010 Dec 8.

  • Researchers investigated iron levels and the protective role of transferrin in rd10 mice, a model of retinal degeneration
  • An X-ray emission experiment found an age-dependent iron accumulation in rd10 mice
  • Transferrin expression and system exposure in rd10 mice led to significant reduction in retinal cell death

Preclinical Studies of Ocular Gene Therapy

Long-term Efficacy of Ciliary Muscle Gene Transfer of Three sFlt-1 Variants in a Rat Model of Laser-induced Choroidal Neovascularization

El Sanharawi M, Touchard E, Benard R, Bigey P, Escriou V, Mehanna C, Naud MC, Berdugo M, Jeanny JC, Behar-Cohen F. Gene Ther. 2013;20(11):1093-1103.

  • Researchers evaluated the long-term efficacy of gene transfer with 3 soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1) variants in a laser-induced rat model of wet age-related macular degeneration (AMD)

Gene transfer of sFlt-1 variants significantly reduced vascular leakage and neovascularization (NV) at 3 weeks and inhibited NV for up to 6 months

Non-Viral Gene Therapy for GDNF Production in RCS Rat: The Crucial Role of the Plasmid Dose

Touchard E, Heiduschka P, Berdugo M, Kowalczuk L, Bigey P, Chahory S, Gandolphe C, Jeanny JC, Behar-Cohen F. Gene Ther. 2012;19(9):886-898.

  • Glial cell line-derived neurotrophic factor (GDNF) has been proposed as a potential treatment for RP
  • Researchers found gene transfer of a GDNF-encoding plasmid delayed photoreceptor and retinal function loss but accelerated photoreceptor degeneration and loss of electrophysiological response in RCS rats

Suprachoroidal Electrotransfer: A Nonviral Gene Delivery Method to Transfect the Choroid and the Retina Without Detaching the Retina

Touchard E, Berdugo M, Bigey P, El Sanharawi M, Savoldelli M, Naud MC, Jeanny JC, Behar-Cohen F. Mol Ther. 2012;20(8):1559-1570.

  • Researchers described suprachoroidal electrotransfer, a transfection method involving the administration of nonviral plasmid DNA into the suprachoroidal space
  • Experiments in rats found retinal cells were efficiently transduced for at least a month; no ocular complications were recorded

In Vivo Gene Transfer Into The Ocular Ciliary Muscle Mediated By Ultrasound And Microbubbles

Kowalczuk L, Boudinet M, El Sanharawi M, Touchard E, Naud MC, Saïed A, Jeanny JC, Behar-Cohen F, Laugier P. Ultrasound Med Biol. 2011;37(11):1814-1827.

  • Researchers assessed the combinatorial application of ultrasound and microbubbles to transfect the ciliary muscle of rat eyes
  • The combinatorial transfection protocol led to target gene expression at 1 week but significant reductions in expression at 1 month

The Ciliary Smooth Muscle Electrotransfer: Basic Principles and Potential for Sustained Intraocular Production of Therapeutic Proteins

Touchard E, Kowalczuk L, Bloquel C, Naud MC, Bigey P, Behar-Cohen F. J Gene Med. 2010;12(11):904-919.

  • Researchers described the development of a nonviral gene therapy method based on the electrotransfer of plasmid in the ciliary muscle
  • The gene transfer procedure produced long-lasting and dose-dependent secretion of encoded proteins in the rat vitreous

Preclinical Studies of Ocular Gene Therapy Targeting TNF-α

Effects of Ciliary Muscle Plasmid Electrotransfer of TNF-Alpha Soluble Receptor Variants in Experimental Uveitis

Touchard E, Bloquel C, Bigey P, Kowalczuk L, Jonet L, Thillaye-Goldenberg B, Naud MC, Scherman D, de Kozak Y, Benezra D, Behar-Cohen F. [Published correction appears in Gene Ther 2009 Aug;16(8):1058: Kowalczuc, L corrected to Kowalczuk, L]. Gene Ther. 2009;16(7):862-873.

  • Researchers described targeting inflammation-related TNF-α protein by transfection of ciliary muscle with plasmids encoding different variants of the p55 TNF-α soluble receptor
  • In a rat model of endotoxin-induced uveitis, transfection resulted in sustained neutralization of TNF-α protein and reduced infiltration of inflammatory cells within the ocular tissue

Local Ocular Immunomodulation Resulting from Electrotransfer of Plasmid Encoding Soluble TNF Receptors in the Ciliary Muscle

Kowalczuk L, Touchard E, Camelo S, Naud MC, Castaneda B, Brunel N, Besson-Lescure B, Thillaye-Goldenberg B, Bigey P, BenEzra D, de Kozak Y, Behar-Cohen F. Invest Ophthalmol Vis Sci. 2009;50(4):1761-1768.

  • Researchers evaluated the efficacy of transfection with a plasmid encoding a p55 TNF-α receptor in a rat model of autoimmune uveoretinitis induced by S-antigen
  • Transfection led to delayed and less severe uveitis, contributing to a reduction in retinal damages

Plasmid Electrotransfer of Eye Ciliary Muscle: Principles and Therapeutic Efficacy Using hTNF-Alpha Soluble Receptor in Uveitis

Bloquel C, Bejjani R, Bigey P, Bedioui F, Doat M, BenEzra D, Scherman D, Behar-Cohen F. FASEB J. 2006;20(2):389-391.

  • Researchers described an electrically-mediated plasmid delivery technique targeted to the ciliary muscle
  • Electrotransfer of chimeric TNF-α soluble receptor inhibited inflammation in rats with endotoxin-induced uveitis, without inducing any ocular pathology or structural damage

Reviews of Ocular Gene Therapy

Ocular Barriers and Their Influence on Gene Therapy Products Delivery

Leclercq B, Mejlachowicz D, Behar-Cohen F. Pharmaceutics. 2022;14(5):998. Published 2022 May 6.

  • Reviewers described the role that ocular barriers play in limiting the bioavailability of gene therapy products while simultaneously mitigating undesirable systemic exposure

Les Anti-TNF-α Pour le Traitement des Uvéites Non Infectieuses [Anti-TNF-α in the Treatment of Non-infectious Uveitis]

Hoogewoud F, Kowalczuk L, Bousquet E, Brézin A, Touchard E, Buggage R, Bordet T, Behar-Cohen F. Med Sci (Paris). 2020;36(10):893-899.

  • Reviewers discussed the potential application of a nonviral gene therapy approach to introduce TNF-α into the eye to treat non-infectious uveitis

Ocular Gene Therapies in Clinical Practice: Viral Vectors and Nonviral Alternatives

Bordet T, Behar-Cohen F. Drug Discov Today. 2019;24(8):1685-1693.

  • A review paper on the current gene therapy strategies (viral and nonviral approaches) for ocular diseases, with a focus on clinical-stage products

Protein Delivery for Retinal Diseases: From Basic Considerations to Clinical Applications

El Sanharawi M, Kowalczuk L, Touchard E, Omri S, de Kozak Y, Behar-Cohen F. Prog Retin Eye Res. 2010;29(6):443-465.

  • Reviewers covered the application of nonviral gene therapy in delivering therapeutic proteins to the eye

Electrically Assisted Ocular Gene Therapy

Bejjani RA, Andrieu C, Bloquel C, Berdugo M, BenEzra D, Behar-Cohen F.. Surv Ophthalmol. 2007;52(2):196-208.

  • Reviewers focused on the basic principles and therapeutic application of electrotransfer and iontophoresis as nonviral gene delivery systems for the treatment of eye diseases

Non-Viral Ocular Gene Therapy: Potential Ocular Therapeutic Avenues

Bloquel C, Bourges JL, Touchard E, Berdugo M, BenEzra D, Behar-Cohen F. Adv Drug Deliv Rev. 2006;58(11):1224-1242.

  • Reviewers described various features and therapeutic potential of nonviral gene therapy in ocular diseases