Objective: To study the protective effects of siponimod on the retina in experimental glaucoma model.
Background: Siponimod is indicated for the treatment of relapsing forms of multiple sclerosis (MS). Selective modulation of the sphingosine 1-phosphate receptor on lymphocytes by siponimod prevents their infiltration into the CNS and thereby functions through an anti-inflammatory mechanism. Apart from its immunosuppressive actions, siponimod is suggested to activate neuroprotective cellular signalling pathways. Chronic optic nerve injury in the form of experimental glaucoma leads to progressive loss of retinal ganglion cells and anterograde trans-synaptic degenerative changes in the higher visual centres. This study aimed to determine the potential protective effects of the drug on the retina in glaucoma conditions.
Methods: Intracameral microbead injections (Fluospheres, 10 µm, weekly) were performed into the anterior eye chamber of C57BL/6 mice that resulted in sustainably increased intraocular pressure (IOP) for 2 months (20-25 mmHg). Siponimod was administered through diet (10mg/kg) to a group of high IOP mice. Inner retinal functional assessment was performed using positive scotopic threshold responses (pSTRs, −4.3 log cd·s/m2) and amplitudes measured 100-120 ms after the initial stimulation. Histological analysis was performed in the retinal sections using hematoxylin and eosin staining.
Results: Mice fed on siponimod diet revealed 4-fold decrease in circulating lymphocytes counts compared to the control diet. No remarkable changes in biochemical analytes were detected in the serum of drug treated animals. Retinal pSTR confirmed that inner retinal function in glaucomatous eyes was decreased in glaucoma conditions. Drug treated animals demonstrated significant (p< 0.001) protection of about 61±6 % in pSTR amplitudes compared to the control high IOP exposed eyes. Histological assessment further supported these findings and revealed preservation of the ganglion cell layer in the siponimod treated group (p< 0.001).
Conclusion: We report that siponimod exhibited a protective effect on retinal electrophysiology and preserved inner retinal structure in experimental glaucoma. Our ongoing investigations will reveal potential biochemical mechanisms underlying these effects in the retina.
Disclosure: The authors have nothing to disclose. This study was supported by Novartis Australia.