Abstract
Introduction: :
Purposes:Both retinal ganglion cell (RGC) apoptosis and retinal nerve fiber layer (RNFL) thinning are assumed to be the first structural changes of glaucoma. The aim of this study is to describe simultaneously the natural history of RGC apoptosis and modifications in the RNFL and other retinal layers in a rat model of glaucoma using state-of-the-art imaging technologies.
Methods: :
Dark Agouti (DA) male rats (n = 20) with surgically-induced chronic ocular hypertension (OHT) in the left eye were imaged using in vivo methods previously established. RGC apoptosis was estimated using DARC and measurements of RNFL, inner plexform layer (IPL), and inner nuclear layer (INL) thickness were achieved at the same time using a customized OCT Spectralis (Heidelberg Engineering). Imaging was carried out in vivo at baseline, 3 and 8 weeks after IOP elevation.
Results: :
Baseline (BL) measurements showed local change in the RNFL, in the order: temporal (T, 40.26±3.38 µm), supero-temporal (ST, 40.25±2.29 µm), nasal (N, 35.84±1.65 µm), supero-nasal (SN, 32.46±3.69 µm), infero-nasal (IN, 36.62±3.21 µm), and infero-temporal (IT, 31.94±3.00 µm). Regional variation was not evident at BL in the IPL and INL.RGC apoptosis, assessed by DARC, achieved peak levels at 3 weeks following OHT surgery. Reduction in whole retinal thickness was shown at 3 (14.3%, p<0.001) and 8 weeks (16.2%, p<0.001) compared to BL. We have shown also a thinning of the inner retinal layers (p<0.01) with shrinkage of 36.4%, 15.9% and 15.5% in the RNFL, IPL & INL at three weeks and 35.8%, 15.2% and 14.4% at 8 weeks respectively.
Conclusions: :
Our results show that the maximal RGC apoptosis arises simultaneously with documented significant alterations in the RNFL in experimental glaucoma. Significant decreases in INL and IPL thickness suggests retinal neurons other than RGCs, such as bipolar, horizontal and amacrine cells may be also be affected in the early stages of glaucoma in this model. Further work is needed to delineate the relationship of these events to each other and to functional changes. However, these results highlight the advantages of monitoring real time parameters through imaging and of recording both cellular (DARC) and tissue changes in the retina (OCT) in glaucoma models - methodologies that due to their non-invasive nature, can be easily applied to the patient.
Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • imaging/image analysis: non-clinical • image processing