The pathology of glaucoma is still subject to research. In general, it is considered a multifactorial, heterogeneous group of ocular diseases and is the second most common cause of human blindness worldwide.
1 Furthermore, it is defined by a progressive and irreversible loss of retinal ganglion cells (RGCs) and their axons,
2 which leads to visual field loss in more advanced stages.
3 Glaucoma is often associated with an elevated intraocular pressure (IOP),
4 but solely 60% to 75% of the patients who suffer from primary open angle glaucoma (POAG) show an IOP elevation of more than 21 mm Hg.
5 Several studies have demonstrated that an elevated IOP does not remain at a stable level, but rather that it underlies strong dynamics including IOP fluctuations, pressure peaks, and circadian variations of approximately 10% to 20% (up to ±4 mm Hg).
6–8 Moreover, there are hints of a relationship between IOP fluctuations and increased mean IOP, which further impacts the visual field.
9–12 While half of these studies indicate a direct link to disease progression, others do not. On the other hand, the remaining 25% to 35% of the glaucoma patients suffering from normal tension glaucoma manifest glaucomatous symptoms without significant elevation of the IOP.
13 Nevertheless, an elevated IOP level is still considered a major risk factor. Diagnosing glaucoma is based on anamnesis, IOP measurement, perimetry, and imaging methods. Using optical coherence tomography (OCT) and confocal scanning laser technology, glaucomatous alterations, such as an increase of papillary excavation, bended vessels at the disc margin, decrease of the retinal thickness, and optic disc hemorrhages in 3% to 6% of the cases, can be detected and monitored. As glaucoma is a slow, progressive neurodegenerative disease, already 20% to 40% of the RGCs are irreversibly marred by the time of clinical diagnosis.
14 By now, numerous different hypotheses concerning the pathogenesis exist, but none is sufficient to elucidate the disease pattern on its own. It is assumed that the interaction of individual pathomechanisms, such as IOP-dependent and IOP-independent dysregulations of the ocular blood flow and retinal ischemia, lead to the final loss of RGCs. These pressure-induced dysfunctions and autoregulations in retinal blood vessels often lead to RGC loss by, for example, anoxia and reperfusion injury.
15,16 Currently, there are several methods for inducing invasive and chronic experimental IOP elevations in laboratory animals, such as injection of hypersaline sodium chloride solution into the episcleral vein
17 or its cauterization,
18 injection of microparticles into the anterior chamber,
19 and laser photocoagulation to the trabecular meshwork.
20 However, these models provide a static IOP elevation, which does not comply with the IOP dynamics in POAG patients and, therefore, a model enabling dynamic IOP adjustments is needed. The first such model reported was that of Joos et al.,
21 who adjusted a loop around the eyeball of a rat in a kind of oculopression for intermittent, short-term, minimally invasive IOP elevation, with a strong potential to conduct arbitrary IOP elevation. Another method based on cup suction oculopression initially described by Ulrich and Ulrich,
22 has been developed for the determination of ophthalmic artery blood pressure in humans and rabbits and might be suitable for arbitrary IOP elevation in rats as well. Therefore, the present study aimed at examining both methods to study a slow, progressive RGC loss model by recurrent short-term IOP elevations and investigated its IOP dynamics during unilateral manipulation. To simulate a variable IOP profile with fluctuations from physiologic IOP to pressure peaks comparable to those of POAG patients, an accumulation of 30 hours of IOP elevation was scheduled for a timespan of 6 weeks. The elevation was performed in rat eyes to an estimated glaucomatous IOP level above 30 mm Hg. The potential glaucomatous effects in the retina, such as thinning of the retinal thickness due to RGC loss, were assessed by OCT and verified by RGC density analysis via Brn3a immunostaining in cross-sections. Enhanced RGC quantification was performed by optic nerve axon counting. As a new and innovative approach, OCT imaging was combined with the loop-adjusted oculopression method described by Joos et al.
21 For the first time, this might offer the possibility of real-time in vivo OCT imaging to investigate alterations of the retinal constitution during IOP pressure changes.