Long-Term Effects of a Photodisruptive Laser-Induced Traumatic Neuropathy Model.

Purpose: To create a mouse traumatic optic neuropathy (TON) model that is reproducible, reliable, and easy to manipulate with high specificity to retinal ganglion cell (RGC) layer and no mortality. The model will be useful for understanding the pathophysiology of retinal ganglion cell death and for testing neuroprotective therapeutics.

Methods: An Nd:YAG laser was used to generate focal photodisruptive retinal damage. Noninvasive in vivo ophthalmologic imaging technologies such as optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (CSLO) were used to longitudinally track the retinal nerve fiber layer (RNFL) thickness and RGC number change, respectively. Immunostaining and pattern electroretinography (PERG) were also used to evaluate structure and functional change after laser injury.

Results: Our ND:YAG laser generates a concussive photodisruptive laser shockwave force which induces focal RGC death in the targeted area. We observed a correlative decrease in RGCs number, RNFL, and PERG function of RGC in the laser zone. The pattern of RNFL thinning and RGC soma loss correlates with the pattern and amount of fluorescence loss on OCT and CSLO images, respectively. The ND:YAG laser does not cause any damage to other layers in the retina nor any side effects including changes in intraocular pressure, corneal edema, and calcification or mortality (which has been observed in other TON models).

Conclusions: We have created a new and novel RGC TON death model that confers no mortality and produces a quantifiable decrease in RGC number and function. The laser targeted regions of the retina correlate with both in vivo imaging by OCT and CSLO and histologically with regions of RGC loss without ophthalmic side effects.

Translational Relevance: This laser-based TON injury model is simple to implement, is reproducible, and is useful for determining the molecular and cellular pathophysiology of TON and RGC death and for testing neuroprotective therapeutics.