Sigma 1 Receptor in Astrocyte-Mediated Retinal Ganglion Cell Neuroprotection in Glaucoma

Article: Protein protects brain cells most impacted by glaucoma
Source: Medical College of Georgia at Augusta University
Published: March 1, 2022

 Retinal ganglion cells grown with wild-type optic nerve head astrocytes (center) showed increased neurite outgrowth compared to those grown without astroctyes (left) and with astrocytes missing the sigma 1 receptor (right) after 7 days

Sigma 1 receptor (S1R) is a unique and ubiquitous protein in neuronal and glial cells of the nervous system, including in the retinal ganglion cells (RGCs) and astrocytes of the optic nerve, which transmits visual signals from the retina to the brain. Although not fully understood, S1R is thought to interact with numerous other proteins to promote homeostasis in the nervous system. Researchers studying the role of S1R in the optic nerve head found that cell cultures where S1R was present on astrocytes contributed to the growth and survival of their associated RGCs, even when these two cell types were not physically in contact. (Astrocytes in vivo have a very tight hold around the neurons they support.) Specifically, the scientists compared total and maximal neurite length, neurite root, and extremity counts between wild-type (WT) RGCs cocultured with either WT or S1R knockout (S1R KO) optic nerve head astrocytes (ONHAs), as measured at 2, 4, or 7 days. They found a consistent trend of decreased total and maximal neurite length and decreased root and extremity counts for RGCs grown with S1R KO astroctyes compared to WT astrocytes, strongly suggesting the critical role of S1R in the growth of RGCs. Similarly, apoptosis increased in ONHAs that were missing S1R compared to WT ONHAs. In other words, the sigma 1 receptor itself is essential to the function of the astrocytes, for example, secreting supportive factors for neurons like brain-derived neurotrophic factor and increasing the activity of synapses in the optic nerve head. This protective effect occurs even when RGCs are in the same medium where astrocytes with intact S1R had been, even after these support cells were not present. The researchers hope that their findings will aid in the discovery and development of drugs, such as the pain reliever (+) – pentazocine, that activate the sigma 1 receptor, thereby conferring neuroprotection in diseases like glaucoma and informing the study of other neurodegenerative diseases such as Alzheimer's and multiple sclerosis.

My rating of this study: ⭐⭐

Zhao J, Gonsalvez GB, Mysona BA, et al. "Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection." Investigative Ophthalmology & Visual Science.  63(1). February 2022. https://doi.org/10.1167/iovs.63.2.1