Abstract
Introduction: :
The retinal damage induced by laser photocoagulation is multiplied by secondary degeneration processes whereby tissues adjacent to the primary lesion are damaged. NAP is an 8 amino acid peptide derived from activity–dependent neuroprotective protein (ADNP). It exhibits direct neuroprotection in cell culture, animal models (review – J Mol Neurosci. 2004;24:67) and against retinal ganglia cell degeneration associated with nutrient deprivation (IOVS. 2005;46:933). However, no in vivo retinal neuroprotection studies were reported to–date.
Purpose: :
To test the neuroprotective ability of NAP to reduce the spread of laser–induced retinal damage.
Methods: :
Standard argon laser lesions (514 & 544 nm, 200 mm, 0.1 W, 0.05 second) were created in 72 DA pigmented rats divided into four groups: two NAP treated groups (intravenously or intravitreally immediately after the photocoagulation) and two control groups treated similarly by saline. The lesions were evaluated histologically and morphometrically 3, 20 and 60 days after the injury.
Results: :
Preliminary results showed that when administered 24 hours after the lesion, NAP had no effect. In contrast, the immediate intravitreal injection of NAP had significant ameliorative effect (P < 0.01) 3 days after the laser injury. Furthermore, the immediate intravenous administration of NAP reduced the cell loss in the whole lesion at all tested time points, though only sixty days after photocoagulation this reduction was statistically significant (P < 0.01). When measured in the central lesion zone, cell loss was reduced at all the time points. The systemic administration of NAP had also significant ameliorative effect (P < 0.01) on the diameter of the lesion 20 and 60 days after the injury.
Conclusions: :
The results show that systemic treatment with NAP is neuroprotective in vivo on unmyelinated (gray matter) neural tissue such as the retina. The proposed mechanism of NAP’s neuroprotection involves microtubules, key cytoskeletal elements in the living cell, implying a broad protective efficacy (J Biol Chem. 2004;279:28531). The results described above suggest that NAP development may be of clinical significance in the treatment of retinal lesions in humans. The intravenous formulation of NAP, termed AL–208, is under clinical development by Allon Therapeutics that supported this research.
Keywords: neuroprotection • laser • cytoskeleton