Eyes open to the causes of blindness
Some retinal diseases lead to photoreceptor degeneration, while the rest of the retina is initially left intact. This suggests that retinal circuitry plays a major role in the development of retinal diseases by leaving important areas exposed to harmful environmental effects. The EU-funded RETICIRC (Circuit specific approaches to retinal diseases) initiative has shown that vision can be restored if the degenerated photoreceptors or neurons in the outer retina can be artificially stimulated. Researchers used enhanced knowledge of the structure and function of specific retinal circuits to discover therapies for retinal diseases such as retinitis pigmentosa and glaucoma. RETICIRC focused on examining basic retinal signal processing and tested how photoreceptor degeneration takes place in retinitis pigmentosa by testing the bystander hypothesis. This hypothesis theorises that the more onlookers there are, the less likely any of them will come forward to help in a situation of emergency. Researchers also focused on developing optogenetic techniques to restore light sensitivity in degenerated photoreceptors and nerve cells in the retina. They labelled rod bipolar cells and horizontal cells to find the effects of photoreceptor degeneration on second-order neurons. The team found that abnormally grown dendrites disappeared with increasing age and with progress of degeneration in both transgenic mouse lines used. The team found that photoreceptor degeneration affected the dendritic organisation of horizontal cells and rod bipolar cells in the same way. RETICIRC made significant progress with regard to describing the outer retina, and developed a quantitative model of photoreceptors. The researchers then described the functional properties of specific ganglion cell classes. The team provided a functional description of the feedback pathway from horizontal cells to cones. The researchers then demonstrated that negative feedback along this pathway is done without the mediation of a neurotransmitter. Project scientists restored sensitivity to light in degenerated photoreceptors of mice and also applied the technique on human retinal explants. These accomplishments affirm the RETICIRC consortium’s conviction that the optogenetic strategy represents a viable means of restoring vision.
Keywords
Photoreceptor degeneration, retina, RETICIRC, retinitis pigmentosa, optogenetic
