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Guorong Li, Vibhuti Agrahari, Iris Navarro, Sina Farsiu, Ashim K Mitra, W Daniel Stamer; Pentablock Copolymer Dexamethasone Nanoformulations Induced Ocular Hypertension in Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1659. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of dexamethasone (DEX) encapsulated pentablock copolymer-based nanoparticles (NPs) (DEX.NPs) on intraocular pressure (IOP), plus function, behavior and ultrastructural changes in conventional outflow tissues in mice.
C57BL/6J mice were injected bilaterally with newly developed DEX.NPs or control nanoparticles (CON.NPs) in subconjunctival/periocular space once-twice/week for 2-8 weeks. IOP was measured twice/week with TonoLab Tonometer. Outflow facility was determined by iPerfusion system. Outflow tissue responses to IOP challenges (10-30 mmHg) in vivo were examined by Spectral Domain Optical Coherence Tomography (SD-OCT). Ultrastructural changes in outflow tissues were visualized by Transmission electron microscopy.
The average IOP elevation in DEX.NPs treatment groups over 2 month period was 6.31 ± 0.23 mmHg compared to CON.NPs treatment groups (0.13 ± 0.13 mmHg). Outflow facility significantly decreased after 2-4 weeks DEX.NPs treatment (3.79±0.39 CON.NPs vs. 2.6±0.31 nl/min/mmHg DEX.NPs, p = 0.023). Using OCT, the Schlemm’s canal (SC) lumen demonstrated a higher resistance to collapse following increasing IOP gradients in the DEX.NPs treatment group compared to CON.NPs treatment group. The conventional outflow pathway displayed significant increase basement membrane deposits below the inner wall of SC, and increase collagen fibril content in the trabecular meshwork (TM) in DEX.NPs treated eyes compared to CON.NPs treated eyes.
Subconjunctival/periocular injection of DEX.NPs into mouse eyes induced sustained and IOP level controlled ocular hypertension; decreasing outflow facility; and TM ultrastructural changes that closely resemble human steroid induced ocular hypertension. Increased extracellular deposits in outflow tissues could lead to increase TM stiffness that prevented SC collapse at elevated IOPs.
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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