• Function of neuromodulators in retinal circuitry

Agents such as the neuropeptide somatostatin, dopamine, and nitric oxide (NO) are present in the retina, where they act as neuromodulators. We have established the functional mapping of somatostatin receptors in the retina and the retinal pigment epithelium (RPE) and examined their role in retinal circuitry. We have shown that somatostatin influences dopamine and nitric oxide release and that part of its physiological actions is mediated via a NO/cGMP signalling. Currently we are examining somatostatin’s interactions with the cannabinoid system also found in the retina.

• New Therapeutic Targets for Retinal Disease 

• Models of Retinopathies

Ischemia is the underlying cause of many retinal diseases that leads to visual loss and blindness. A neurodegenerative component is evident in diseases such as diabetic retinopathy and glaucoma.  To date there are no efficacious therapeutics that target the ischemia induced retinal neurodegeneration.

The goal of our studies is to investigate new targets for retinal therapeutics. We are employing ex vivo (chemical ischemia model) and in vivo animal models (AMPA excitotoxicity, STZ-model of diabetic retinopathy) to elucidate the neuroprotective effects of neuropeptides (somatostatin), cannabinoids and most currently neurosteroids (in collaboration with Prof A. Gravanis).

• In the somatostatin project, we have recently shown that Pasireotide (SOM230), a long acting sst1,2,3,5 agonist,  protects retinal neurons in models of retinopathy (chemical ischemia and AMPA excitotoxicity) with high efficacy. It decreased retinal apoptotic cell death as shown by TUNEL FACS analysis. Its pharmacological profile renders it appropriate as a retinal therapeutic (Kokona et al., Exp Eye Res, under revision).
  
• In the cannabinoid project, we have shown than methanandamide, an analog of the endogenous cannabinoid anandamide, and the synthetic CB1/CB2 agonist HU210 protected the retina in the in vivo model of AMPA excitotoxicity via mechanisms that involve both CB1 and CB2 (Kokona et al., unpublished data).
  
• In the neurosteroid project, we have shown that the endogenous neurosteroid DHEA protected the retina in the in vivo model of AMPA excitotoxicity via a mechanism involving the NGF TrkA receptor (Kokona et al., Neuropharmacology, 2012). We also have preliminary data to support the antiapoptotic and neuroprotective effects of DHEA and its novel synthetic analog BNN27 in the STZ model of diabetic retinopathy.
  

An ongoing collaboration with the Ophthalmology Clinic (Prof I. Pallikaris, Prof M. Tsilimbaris) lends credence to the translational potential of the ongoing research.