A new model of axon degeneration in the mouse optic nerve using repeat intraocular pressure challenge.

We characterize a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. C57BL/6J mice were subjected to two acute periods of intraocular pressure (IOP) elevation (50 mmHg for 30 min) by cannulation of the anterior chamber. We used full-field electroretinography and visual evoked potentials (VEPs) to measure subsequent changes in retina and optic nerve function, and histochemical techniques to assess RGC survival and optic nerve structure. In 12 month old mice, a single IOP challenge caused loss and subsequent recovery of RGC function over the following 28 days with minimal cell death and no observed axonal damage. A second identical IOP challenge resulted in persistent RGC dysfunction and significant (36%) loss of RGC somas. This was accompanied by a 16.7% delay in the latency and a 27.6% decrease in the amplitude of the VEP. Severe axonal damage was seen histologically with enlargement of axons, myelin disruption, reduced axon density, and the presence of glial scarring. In contrast, younger 3 month old mice when exposed to a single or repeat IOP challenge showed quicker RGC functional recovery after a single challenge and full functional recovery after a repeat challenge with no detectable optic nerve dysfunction. These data demonstrate a highly reproducible and minimally invasive method for inducing RGC degeneration and axonal damage in mice. Resilience of the optic nerve to damage is highly dependent on animal age. The time-defined nature of functional versus structural loss seen in this model stands to facilitate investigation of neuroglial responses in the retina after IOP injury and the associated evaluation of neuroprotective treatment strategies. Further, the model may be used to investigate the impact of aging and the cellular switch between neurorecovery and neurodegeneration.

Non-optical coherence tomography modalities for assessment of angle closure.

Primary angle closure glaucoma is a leading cause of irreversible blindness, particularly in Asia. Its pathophysiology is based in the closure of the anterior chamber angle (ACA). In addition to gonioscopy (current reference standard), in the past decade, anterior segment optical coherence tomography (AS-OCT) has been incorporated in routine ophthalmic practice to help assess the configuration of the ACA. Especially in nonspecialist ophthalmology practice, gonioscopy may be less frequently performed and AS-OCT may not be available, leading to the need of other anterior segment evaluation methods. Evaluating the anterior chamber depth (ACD) has long been recognized as screening tool for primary angle-closure glaucoma. It can be measured with several devices, such as Scheimpflug photography and the scanning peripheral ACD analyzer. It can also be estimated with the oblique flashlight test and van Herick technique (limbal ACD assessment). More recently, goniophotographic systems have been developed to produce images of the ACA similar to those seen with manual gonioscopy. NGS-1 automated gonioscope (NIDEK Co, Gamagori, Japan) and the RetCam (Natus Medical Incorporated, Pleasanton, CA) are commercially available. However, NGS-1 is the only one with a specialized software for ACA imaging. Several prototype devices are currently being developed, such as the GonioPEN and axicon lens assisted gonioscopy. This article aims to review different modalities of ACA assessment, beyond AS-OCT, and compare their relative advantages and disadvantages.