Modeling Human Glaucoma: Lessons from the in vitro Models

Abstract

Glaucoma, a leading cause of blindness worldwide, is a degenerative disease characterized by retinal ganglion cell (RGC) loss and optic nerve atrophy. Elevated intraocular pressure (IOP) is a main risk factor for onset and progression of the disease. Since increased IOP is the only modifiable risk factor, relevant models for glaucoma would comprise RGC and optic nerve damage triggered by ocular hypertension. Animal models of glaucoma have greatly contributed to the understanding of the molecular mechanisms of this pathology, and they have also facilitated the development of new pharmacological interventions. Although animal models of glaucoma have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. There is a recognized demand for in vitro models that can replace or reduce the need for animal experiments. Several in vitro models have emerged as a great opportunity in the field of glaucoma research, helping to clarify the mechanisms involved in disease progression. Several types of equipment have been developed to expose cells and tissue cultures to elevated pressures. Herein, we discuss the methodology used to increase pressure, the main findings, and the relevance of in vitro models for the study of the pathophysiology of glaucoma.

Blockade of microglial adenosine A2A receptor suppresses elevated pressure‐induced inflammation, oxidative stress, and cell death in retinal cells

“…Elevated intraocular pressure is the main risk factor of glaucoma (Almasieh et al, ). In this work, cultures have been exposed to EHP in order to mimic elevated intraocular pressure in vitro (Aires et al, ). In our conditions, an increase in hydrostatic pressure induced upregulation of A 2A R in microglia suggesting that microglia react to changes in pressure and A 2A R may modulate the response of microglia to elevated pressure.…”

“…However, the specific role of microglial cells was not addressed, as well as the impact of A 2A R blockade in microglial cells in the context of glaucoma. Since elevated intraocular pressure is considered the main risk factor of glaucoma, we focused on the contribution of microglia to the death of retinal neurons under elevated pressure to model glaucoma in vitro (Aires, Ambrósio, & Santiago, ). In addition, we also studied whether the pharmacological blockade or the genetic inactivation of A 2A R in microglia could attenuate the inflammatory profile of microglia, using a murine microglia cell line, primary retinal microglia cultures, rat retinal neural cell cultures, and human retinal tissue exposed to elevated pressure.…”

In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs

“…33, 34 However, each animal model presents unique challenges. Non-human primate models, though having a close resemblance to human anatomy and cellular organization, have limitations in terms of economics and practicality.…”

A lab-on-a-chip model of glaucoma

“…Pressure chambers are important tools to study the influence of elevated pressure on individual cell types (Aires et al, 2017). Prior to employing animal models, they allow the assessment of pre-defined experimental conditions and evaluation of specific variables contributing to cell survival.…”