Contribution of intraocular pressure‐dependent and pressure‐independent glaucoma models to neuroprotection

Abstract

AbstractGlaucoma is considered a heterogeneous group of degenerative optic neuropathies characterized mainly by an ongoing loss of retinal ganglion cells (RGCs) which causes progressive deterioration of the visual field and irreversible blindness. The aetiology and pathophysiology of glaucoma are not known in detail and are a matter of debate. Although the most significant risk factor in the development and progression of glaucoma correlates with elevated intraocular pressure (IOP), at present the only treatment available to prevent or delay its development is to reduce IOP by medication or surgery to slow its detrimental effects. But reducing IOP alone does not stop the progression of the disease. Therefore, IOP may not be the only motive for glaucomatous retinopathy and optic neuropathy, and there could be other hidden mechanisms contributing to the loss of RGCs.A suitable animal model of neurodegenerative disease, such as glaucoma, should be easy to induce and reproduce, feasible and predictable, and allow detection and quantification at the biochemical, morphological and functional levels of the induced pathological changes. However, no model emulates all aspects of a pathology such as glaucoma, which is likely to have more than one aetiology and manifest itself through different pathological mechanisms. Hence, the interest and need to establish and use different experimental models in rodents to improve our understanding of the pathophysiology of glaucoma and to investigate possible neuroprotective agents. In general, experimental models of glaucoma established in rodents involve a transient or chronic increase in IOP above normal values, which allows us to study the pathological changes associated with ocular hypertension. However, elevated IOP may not be the only cause of glaucomatous retinopathy and optic neuropathy, hence the need for models that do not involve an increase in intraocular pressure to deal with specific issues of the evolution of this pathology, such as optic nerve injury, retinal ischaemia/reperfusion, intravitreal injection of excitatory amino acids or endothelin‐induced optic neuropathy.Results obtained in different experimental models of glaucoma mimicking ocular hypertension or optic nerve damage have confirmed the existence of morphofunctional differences in the time course of RGC loss, both between different types of RGCs and between different lesions. As well as the effects on other retinal cell populations. In this regard, in the outer retina, there is a significant contrast between damage caused by ocular hypertension and optic nerve injury. Both axotomy and ocular hypertension induce a selective loss of RGCs, but ocular hypertension also promotes a loss of photoreceptors.Thanks to the different glaucoma models studied, the findings obtained have contributed to improving our knowledge of glaucomatous pathology and to the development of future neuroprotective therapies.