The Spectral-Domain Optical Coherence Tomography Findings Associated with the Morphological and Electrophysiological Changes in a Rat Model of Retinal Degeneration, Rhodopsin S334ter-4 Rats

Abstract

Purpose To characterize the spectral-domain optical coherence tomography (SD-OCT) findings of the rhodopsin S334ter transgenic rats (line 4) in relation to the morphologic and electroretinographic features. Materials and Methods Rhodopsin S334ter transgenic rats (line 4) were employed as a model of retinal degeneration. The Sprague-Dawley (SD) rats were used as a wild-type control. SD-OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA) was performed on the S334ter rats (line 4) from postnatal days (P) 13−110. The longitudinal changes of the SD-OCT images were analyzed both qualitatively and quantitatively in comparison to those of SD rats. The SD-OCT images were also compared to the histological and electron microscopic findings from examination performed on P 22, 36, and 61. Full field combined rod and cone electroretinography (ERG) was performed and the relationship between the thickness of the retinal sublayers and the amplitudes of the a- and b-waves was further analyzed. Results The photoreceptor inner and outer segment layer became diffusely hyperreflective in the SD-OCT images of the S334ter rats; these findings were not observed in the SD rats. This hyperreflective change corresponded to the degenerated inner and outer segments and the accumulation of the extracellular vesicles in the interphotoreceptor matrix. Quantitatively, the retinal outer sublayer and the photoreceptor sublayer in the S334ter rats became progressively thinner in comparison to those in the SD rats; the difference was statistically significant. The amplitudes of both the a- and b-waves on ERG were severely deteriorated in the S334ter rats. Discussion The SD-OCT images in the S334ter rats noninvasively provided information regarding the pathological changes in the photoreceptors and the longitudinal changes of both qualitative and quantitative changes during retinal degeneration in the S334ter rats (line 4). The pathological features of the photoreceptor inner and outer segments can be detected on SD-OCT as diffuse hyperreflective changes in the photoreceptor layer.

The qualitative assessment of optical coherence tomography and the central retinal sensitivity in patients with retinitis pigmentosa

“…Based on the results from previous animal experiments regarding the relationship between the histologic and ultrastructural findings of photoreceptor degeneration and corresponding SD-OCT features [25][26][27][28][29][30], we classified patients' horizontal and vertical sections of SD-OCT images into five severity grades mainly focused on the structure of the IS/OS layer. The definition of these five grades were as follows: grade 1, almost normal foveal structure or a sharply defined IS-EZ and IZ at the foveal center; grade 2, partial hyperreflective change in the IS/OS layer of the foveal region or a broadened IZ and/or IS-EZ without merging; grade 3, diffuse hyperreflective changes in the IS/OS layer or broad IS-EZ changes in the foveal region or merging of the broadened IS-EZ and IZ; grade 4, remnants of the IS/OS-like structure on the retinal pigment epithelium (RPE); grade 5, absent IS/OS-like structure.…”

“…To overcome these points, animal models harboring homologous genetic mutations to human RP patients may provide some clues for understanding the relationship between SD-OCT images and their histopathological backgrounds caused by photoreceptor degeneration [25]. Based on these speculations, the findings from previously performed animal experiments have enabled us to correlate the pathological findings of photoreceptor degeneration with the findings from SD-OCT [25][26][27][28][29][30]. Common findings in model animals for human RP associated with various kinds of gene mutations include diffuse hyperreflective changes in the photoreceptor inner and outer segments (IS/OS) layer and thinning of the outer nuclear layer (ONL) [25].…”

A spectral-domain optical coherence tomographic analysis of Rdh5-/- mice retina

“…SD-OCT and fundus photography were performed by the methods as described in detail previously, using a Micron 1 IV, Image-Guided 830 nm OCT (Phoenix Retinal Imaging System, Phoenix Research Labs, Pleasanton, CA, USA) [22,23,25,27]. In brief, SD-OCT and fundus photography were carried out at 6 points of time from postnatal-month (PM) 1 to PM6 for both Rdh5 -/and C57BL/6J mice.…”

“…The inner retinal layer A consisted of the retinal nerve fiber layer (NFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL) and the inner nuclear layer (INL); the outer retinal layer B consisted of the outer plexiform layer (OPL) and the outer nuclear layer (ONL); the photoreceptor segments layer C consisted of the photoreceptor inner segment (IS) and outer segment (OS) layers; and combined RPE and the choroid layer (D) (S1 Fig). As previously reported [23,25,27], we measured the thickness of layers A, B, C and D using the InSight 1 software program (Phoenix Research Labs). The borderline between each layer was automatically identified by the software program using the SD-OCT images and was manually modified by the researchers when necessary.…”

“…Although SD-OCT is a noninvasive technology that allows us to investigate the morphological characteristics of various retinal diseases [20,21], it is impossible to directly evaluate the pathological features. In contrast, animal models associated with known gene mutations provide strong evidence that facilitate our understanding of the relationship between the SD-OCT findings and the pathological background [22][23][24][25][26][27][28][29][30][31][32]. However, to our knowledge, no study has assessed the relationship between SD-OCT findings and the origin of the structural changes in Rdh5 -/mice.…”