June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Pigment epithelium-derived factor (PEDF) based therapy induced photoreceptor survival by stabilising the neovessels in a VEGF overexpression CNV rat model
Author Affiliations & Notes
  • Alexander Viktor Tschulakow
    Molecular mechanisms driving age-related macular degeneration Lab, Experimental Vitreoretinal Surgery Group, Center for Ophthalmology, Universitatsklinikum Tubingen, Tubingen, Baden-Württemberg, Germany
    STZ OcuTox, Preclinical Drug Assessment, Hechingen, BW, Germany
  • Lei Xi
    Division of Experimental Vitreoretinal Surgery, Center for Ophthalmology, Universitatsklinikum Tubingen, Tubingen, Baden-Württemberg, Germany
  • Ulrich Schraermeyer
    Division of Experimental Vitreoretinal Surgery, Center for Ophthalmology, Universitatsklinikum Tubingen, Tubingen, Baden-Württemberg, Germany
    STZ OcuTox, Preclinical Drug Assessment, Hechingen, BW, Germany
  • Sylvie Julien-Schraermeyer
    Molecular mechanisms driving age-related macular degeneration Lab, Experimental Vitreoretinal Surgery Group, Center for Ophthalmology, Universitatsklinikum Tubingen, Tubingen, Baden-Württemberg, Germany
    STZ OcuTox, Preclinical Drug Assessment, Hechingen, BW, Germany
  • Footnotes
    Commercial Relationships   Alexander Tschulakow STZ OcuTox, Code E (Employment); Lei Xi None; Ulrich Schraermeyer publication number: 20220133866, Code P (Patent); Sylvie Julien-Schraermeyer None
  • Footnotes
    Support  Dr. Werner Jackstädt-Stiftung
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1133. doi:
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      Alexander Viktor Tschulakow, Lei Xi, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer; Pigment epithelium-derived factor (PEDF) based therapy induced photoreceptor survival by stabilising the neovessels in a VEGF overexpression CNV rat model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1133.

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

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Abstract

Purpose : Pathological choroidal neovascularization (CNV) characterized by abnormal unfunctional, leaky vessels, can cause vision impairment or even blindness. There is evidence linking the anti-vascular endothelial growth factor (VEGF) therapy to severe local and systemic side effects. Additionally, resistance to anti-VEGF therapy has been reported. Thus, novel therapies are still needed. Previously, using wet age-related macular degeneration (AMD) donor eyes, we found that a functional, quiescent CNV can help photoreceptors to survive. Recently, a potential protective effect of quiescent CNV on the RPE and overlying neurosensory retina has been also described in patients. Therefore, stabilizing a CNV instead of removing it could be an innovative alternative to treat wet AMD. A very promising candidate is the pigment epithelium-derived factor (PEDF), a well-known multifunctional protein with antiangiogenic, neuroprotective and also capillary stabilizing properties.

Methods : Intravitreal treatments of PEDF protein alone or combined with bevacizumab were investigated using our previously established CNV rat model, induced by overexpression of VEGF. Bevacizumab alone-, vehicle- and untreated eyes served as controls. The eyes were analyzed using scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) and histologically using light and electron microscopy (EM).

Results : SLO/OCT analyses revealed that bevacizumab and PEDF+bevacizumab treatments reduced the CNV lesion thickness, as expected. Interestingly, PEDF and PEDF+bevacizumab treatments induced a rescue from the retina thickness loss. Moreover, the analysis of the ratio of the ONL area/CNV lesion area showed a survival of the photoreceptors at the CNV site after treatment with PEDF and PEDF+bevacizumab. Further, EM analysis showed that PEDF preserved and stabilized blood vessels and made them tight.

Conclusions : The use of PEDF protein alone or combined with an anti-VEGF agent supports the coordinated growth of new functional CNV vessels and may be an effective strategy for rescuing photoreceptor cells in wet AMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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