Animal models are critically important for understanding the pathophysiology of glaucoma. Yu et al. (1004) have developed a new/modified model of increased episcleral venous pressure (EVP) that raises intraocular pressure (IOP) by directly ligating episcleral veins with nylon suture in rats. The authors ligate three episcleral vein trunks and branches of the other episcleral vein trunks to increase IOP. IOP went from a control baseline of approximately 20 mmHg to 30 mmHg one day post-operatively to a relatively stable range of approximately 27-25 mmHg out to 7 months. In 59.2% of the treated rats, the IOP dropped to less than 24 mmHg within 2-4 weeks and required religation of episcleral veins to maintain ocular hypertension. These elevated IOP success rates compare favorably with other ocular hypertension rate models based on elevated EVP, such as injection of hypertonic saline into1 and cautery of 2 episcleral veins, although the magnitude of IOP elevation and RGC loss appears less with this approach.
The authors also validate their model for glaucoma studies by demonstrating that this persistently elevated IOP (which is milder than in some of the other models) is sufficient to result in selective loss of retinal ganglion cells (RGC) through induction of apoptosis. Moreover, the authors show the pattern of RGC loss is mainly in the peripapilary region of the retina and that Muller cells are affected by ocular hypertension relative to expression levels of GFAP and p27Kip1. Lastly, the authors show that neurotrophic factors such as CNTF and basic FGF are down-regulated in these rat retinas in association with ocular hypertension and RGC loss. Thus, the authors have not only characterized this model on a structural and cellular level but have also shown functional molecular effects of the IOP elevation on the rat retina.
The importance of this new approach for inducing chronically elevated IOP in rats is that it may be a technically simpler than injection of hypertonic saline and cautery of episcleral veins. Validation of this technique by other research groups will be necessary to support the claims of the authors that this approach may give longer and more stable IOP elevation than the other increased EVP ocular hypertension models. In addition, the use of visible nylon sutures makes it simpler to determine on repeat treatment which vessels to ligate and to determine if venous blood flow has been stopped to maintain IOP elevation. Inflammation caused by the injection of hypertonic saline or by laser treatment (in the translimbal laser method of Quigley and colleagues) may influence the activation of cytokines and neurotropic factors which can affect RGC survival and stress responses to increased IOP. The milder chronic IOP elevation and ligature of the episcleral veins with suture might not increase intraocular inflammation and may make this a more ideal animal model to study the pure stress effect of IOP on RGC function and survival.