Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres

Mimicking chronic glaucoma over 6 months with a single intracameral injection of dexamethasone/fibronectin-loaded PLGA microspheres

“…The count of positive Brn3a cells along with four areas of the retina ( Figure 9A ), showed that the mean number of ganglion cells per linear mm of the retina was not significantly different in non-intervened left eyes in comparison to right eyes injected with dexamethasone-fibronectin microspheres ( p = 0.92) ( Figure 9B ). However, fewer ganglion cells per linear mm of the retina were counted (10.12 ± 4.99) than in our previous model (12.16 ± 3.37) at 6 months (Rodrigo et al., 2021 ). In order to ascertain if the injected microspheres were located at the iridocorneal angle, they were analyzed using Hematoxylin/Eosin, Nomarski and fluorescent microscopy.…”

“…Fibronectin has a RGD loop that is a promiscuous site for many cellular integrins, such as α5β1, α3β1, α8β1, and αvβ3 (Pankov & Yamada, 2002 ). This could explain how, unlike our other models where microspheres without fibronectin were injected (Garcia-Herranz et al., 2021 ; Rodrigo et al., 2021 ), focal adhesions were observed between the iris and the cornea ( Figure 11 ). These synechiae are established through the fibronectin-containing microspheres and that would glue the iris and cornea ( Figure 11 ).…”

“…The model presented in this work combines some of the strategies previously used in other rodent models of glaucoma, such as physical blockage of the trabecular meshwork, the administration of corticosteroids or the increased deposition of the protein fibronectin in the extracellular matrix of the trabecular meshwork (Roberts et al., 2020 ; Rodrigo et al., 2021 ). It was decided to co-release dexamethasone and fibronectin as the former stimulates extracellular matrix production and inhibits debris clearance (Dismuke et al., 2016 ; Zeng et al., 2020 ) and on the other hand, fibronectin deposition has been associated with ocular aging and glaucoma progression by playing an important role in trabecular meshwork occlusion in human glaucoma (Babizhayev & Brodskaya, 1989 ; Kasetti et al., 2017 ).…”

“…The weekly injection of blank microspheres produced a sustained and prolonged ocular hypertension (OHT) over six months due to a progressive physical blockage of the trabecular meshwork. This maintained OHT produced a very progressive degeneration of the retina (Garcia-Herranz et al., 2021 ; Rodrigo et al., 2021 ). In a second study, dexamethasone loaded PLGA microspheres also generated OHT and neuroretinal degeneration by only two times injections (Rodrigo et al., 2021 ).…”

“…This maintained OHT produced a very progressive degeneration of the retina (Garcia-Herranz et al., 2021 ; Rodrigo et al., 2021 ). In a second study, dexamethasone loaded PLGA microspheres also generated OHT and neuroretinal degeneration by only two times injections (Rodrigo et al., 2021 ). After those initial approaches, in the present work, we propose a new model of chronic glaucoma produced by intracameral injection of dexamethasone/fibronectin co-loaded PLGA microspheres.…”