June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Therapeutics of stem cell secretome in dexamethasone-induced ocular hypertension mice
Author Affiliations & Notes
  • Yiqin Du
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Ajay Kumar
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Yiqin Du University of Pittsburgh, Code P (Patent); Ajay Kumar University of Pittsburgh, Code P (Patent)
  • Footnotes
    Support  NIH Grant EY025643; P30-EY08098; Research to Prevent Blindness; Eye & Ear Foundation of Pittsburgh.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2646. doi:
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      Yiqin Du, Ajay Kumar; Therapeutics of stem cell secretome in dexamethasone-induced ocular hypertension mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2646.

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

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Abstract

Purpose : Glaucoma is a leading cause of irreversible blindness worldwide. Stem cell-free therapy using stem cell secretome offers great hope for vision restoration. We investigated the protective roles of secretome from trabecular meshwork (TMSC) in dexamethasone (Dex) treated trabecular meshwork (TM) cells and Dex-induced ocular hypertension (OHT) mice.

Methods : Primary human TM cells were treated with 100nM Dex for 5 days and added TMSC secretome to be treated for another 5 days. For Dex-induced OHT, adult C57BL/6 mice were periocularly injected with 20 µl of Dex-acetate (Dex-Ac) at 10 mg/ml weekly for four weeks. Then the mice were periocularly injected with concentrated secretome from TMSC or corneal fibroblasts as well as Dex-Ac weekly for another 4 weeks and waited for 2 weeks before sacrifice. Immunofluorescent staining and qPCR were used to quantify expression levels of glaucoma-associated proteins/genes Myocilin (MYOC) and ANGPTL7. Intraocular pressure (IOP) was measured weekly by I-care tonometer. Statistical analysis was done using one-way ANOVA followed by Tukey posttest. P<0.05 was set as statistically significant.

Results : Both TMSC and fibroblasts showed high viability after 48-hr serum starvation and secretome harvesting, indicating good quality of secretome collection. TM cells had increased Myoc expression after Dex treatment, which was prevented and reversed by TMSC secretome. The increased expression of both Myoc and ANGPTL7 in response to Dex was significantly reduced by all three TMSC secretomes. CHI3L1 expression was diminished after Dex, which was preserved after TMSC secretome treatment. In OHT model, periocularly injected TMSC secretome successfully reduced the IOP elevation from week 4 (13.8±1.8 mmHg) after a single dose, as compared to Dex-treated mice (15.8±3.3 mmHg) and maintained to normal range till the end of the experiment at week 8, similar to that of vehicle controls. Fibroblast secretome was not able to reduce IOP (16.2±2 mmHg and 15.3±1.4 mmHg on week 4 and week 8 respectively), that was at similar levels to Dex-treated mice (week 4, 15.8±3.3 mmHg and week 8, 15.2±1 mmHg). Retinal ganglion cell function was preserved as evaluated by pattern electroretinography.

Conclusions : TMSC secretome protected both Dex treated TM cells and OHT mice by periocular injection. It opens an avenue for stem cell-free therapy for glaucoma with minimum invasive procedures.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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