The role of retinal ganglion cell structure and function in glaucoma

Glaucoma is a multifactorial eye disease defined by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, leading to irreversible vision loss.  Glaucoma poses significant clinical and public health challenges. While elevated intraocular pressure (IOP) remains a significant risk factor and therapeutic target, it is becoming increasingly apparent that other factors may play a role in the disease’s pathogenesis and progression. The structure and function of RGCs, which serve as the ultimate output neurons of the retina and transmit visual information to the brain, are among the most crucial components being studied. This study provides distinct insights into the foundations of glaucoma and potential avenues for intervention and treatment. 

RGC apoptosis and axonal loss within the inner retina may lead to the earliest signs of glaucoma and exhibits a direct correlation with the clinical severity of the disease.  Apoptosis plays an essential role in maintaining homeostasis (balance) during normal development and aging; however, pathologic apoptosis is associated with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and neurodegeneration (as in glaucoma). Other mechanisms can contribute to RGC damage, including elevated IOP, impaired mitochondrial activity, oxidative stress, activation of glial cells, and excitotoxicity.

In the human retina, a variety of RGCs are present, each specializing in distinct visual functions. It is important to note that certain subtypes of RGCs have varying levels of vulnerability to degenerative alterations in glaucomatous circumstances.  For example, in a pressure-induced environment, midget RGCs, which are primarily associated with the processing of visual information at a high level of detail and evaluation of color, and parasol RGCs, which help to detect motion and changes in light levels, undergo degeneration that begins with the dendritic arbor and concludes with cell soma (body) shrinkage.

With advances in imaging technology such as optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy, and adaptive optics, it is now possible to evaluate RGCs in greater detail. A comprehensive understanding of how RGCs are affected by glaucoma could potentially enable ophthalmologists to provide more precise diagnosis and personalized care to patients.  

Source:   Feng, Kathy Ming, et al. “The Role of Retinal Ganglion Cell Structure and Function in Glaucoma.” Cells, vol. 12, no. 24, Dec. 2023, https://doi.org/10.3390/cells12242797