July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Intravitreal HC-HA/PTX3: A potential novel therapy for proliferative vitreoretinopathy
Author Affiliations & Notes
  • Ajay E. Kuriyan
    Flaum Eye Institute, Univ. of Rochester Med Center, Pittsford, New York, United States
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Hua He
    TissueTech, Inc., Miami, Florida, United States
  • Esdras Arrieta
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Nidhi Relhan
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Jeffrey Peterson
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Chen-Wei Su
    TissueTech, Inc., Miami, Florida, United States
  • Megha Mahabole
    TissueTech, Inc., Miami, Florida, United States
  • Sander R Dubovy
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Harry W Flynn
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Jean-Marie A Parel
    Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, United States
  • Scheffer C G Tseng
    TissueTech, Inc., Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Ajay Kuriyan, None; Hua He, Tissue Tech (E), Tissue Tech (P); Esdras Arrieta, None; Nidhi Relhan, None; Jeffrey Peterson, None; Chen-Wei Su, Tissue Tech (E); Megha Mahabole, Tissue Tech (E); Sander Dubovy, None; Harry Flynn, None; Jean-Marie Parel, None; Scheffer Tseng, Tissue Tech (E), Tissue Tech (P)
  • Footnotes
    Support  Bayer Global Ophthalmology Awards Program Grant, NIH, NEI, R44EY025447, R44 EY017497 and R43 EY021045, a research grant from TissueTech, Inc., Miami, Florida, NIH Center Core Grant P30EY014801 and P30EY001319, Research to Prevent Blindness Unrestricted Grant, and the Department of Defense (DOD Grant #W81XWH-09-1-0675)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1157. doi:
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      Ajay E. Kuriyan, Hua He, Esdras Arrieta, Nidhi Relhan, Jeffrey Peterson, Chen-Wei Su, Megha Mahabole, Sander R Dubovy, Harry W Flynn, Jean-Marie A Parel, Scheffer C G Tseng; Intravitreal HC-HA/PTX3: A potential novel therapy for proliferative vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1157.

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

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Abstract

Purpose : Proliferative vitreoretinopathy (PVR), characterized by retinal surface membranes, is the main cause of failure of rhegmatogenous retinal detachments (RRDs). PVR is mediated by proliferation and epithelial mesenchymal transition (EMT) of RPE cells under the influence of vitreous growth factors. Heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) complex is a unique matrix component from amniotic membrane that exerts anti-inflammatory and anti-EMT effects. HC-HA/PTX3 is soluble and can be injected intravitreally. Therefore, we investigated whether HC-HA/PTX3 inhibits rabbit RPE cell proliferation in vitro and evaluated the safety and efficacy of intravitreal HC-HA/PTX3 in an established rabbit PVR model.

Methods : Primary rabbit RPE was isolated using dispase. HC-HA/PTX3 was prepared by our optimized manufacturing procedure. First, we tested if 12.5 to 200 µg/ml HC-HA/PTX3 was toxic to rabbit RPE cells in comparison to HA by the WST-1 assay. Next, we assessed the inhibitory effect of HC-HA/PTX3 on epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2)-induced proliferation in vitro by the WST-1 assay and immunostaining. Then, we tested the safety of intravitreal HC-HA/PTX3 injections using weekly ERGs and fundus exams for four weeks, followed by histologic analysis. Additionally, in New Zealand white (NZW) rabbits, we compared the ability of intravitreal HC-HA/PTX3 and PBS to inhibit PVR, which was induced using gas displacement of vitreous with intravitreal C3F8 and intravitreal injection of NZW RPE cells.

Results : HC-HA/PTX3 (up to 200 µg/ml), similar to HA, is not toxic to unstimulated rabbit RPE cells. EGF+FGF induced a 7-fold increase (p<0.05) in proliferation, which was inhibited in a dose-dependent fashion by HC-HA/PTX3, up to 2.2-fold (p<0.05) with 25 µg/ml. The addition of HA alone did not inhibit proliferation. Two rabbits injected with intravitreal HC-HA/PTX3 did not demonstrate any ERG or fundus exam changes and did not develop any histologic changes. 2 of 4 (50%) rabbits treated with HC-HA/PTX3 developed Grade 3 PVR compared to 7 of 8 (87.5%) of rabbits treated with PBS that developed Grade 3 or worse PVR.

Conclusions : HC-HA/PTX3 is a non-toxic matrix component in vitro and in vivo. HC-HA/PTX3 is a potent inhibitor of RPE cell proliferation and EMT in vitro and inhibits PVR formation in a rabbit model.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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