Quantification of Changes in Visual Function During Disease Development in a Mouse Model of Pigmentary Glaucoma

Grillo, Stephanie L.; Montgomery, Christa; Johnson, Heather M.; Koulen, Peter

doi:10.1097/ijg.0000000000001024

Cited by 12 publications

(15 citation statements)

References 51 publications

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“…Apoptotic RGCs were found as early as in 3-month-old animals [ 21 ]. However, RGC density was shown to remain relatively stable up to 12 months of age [ 32 ], despite a dramatic decrease in visual acuity demonstrated in 11-month-old animals [ 33 ]. Therefore, it seems that RGC degeneration rather than loss and axonal transport failure contribute to the pathological changes in the retina and the optic nerve in these mice at moderately advanced stages of the disease [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some data indicate that pathological processes start earlier than noticeable IOP elevation, even as early as in 3-month-old animals [ 22 , 34 ]. Nevertheless, DBA/2J performance in visual tasks seems similar to C57BL/6 mice at 6 months and significantly decreased when the mice are older [ 33 , 35 ]. Therefore, we selected two timepoints that seem representative for the pathology in this glaucoma model – mice at the early stage of disease (6-month-old) and with moderately advanced glaucoma (10-month-old).…”

Section: Discussionmentioning

confidence: 99%

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Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma

Fiedorowicz

Chorągiewicz

Turski

et al. 2021

IJMS

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Background: It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina. This study aimed to verify the hypothesis that alterations of tryptophan (TRP) metabolism in DBA/2J mice is not limited to the retina. Methods: Samples of the retinal tissue and serum were collected from DBA/2J mice (6 and 10 months old) and control C57Bl/6 mice of the same age. The concentration of TRP, KYNA, kynurenine (KYN), and 3-hydroxykynurenine (3OH-K) was measured by HPLC. The activity of indoleamine 2,3-dioxygenase (IDO) was also determined as a KYN/TRP ratio. Results: TRP, KYNA, L-KYN, and 3OH-K concentration were significantly lower in the retinas of DBA/2J mice than in C57Bl/6 mice. 3OH-K concentration was higher in older mice in both strains. Serum TRP, L-KYN, and KYNA concentrations were lower in DBA/2J than in age-matched controls. However, serum IDO activity did not differ significantly between compared groups and strains. Conclusions: Alterations of the TRP pathway seem not to be limited to the retina in the murine model of hereditary glaucoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma

Fiedorowicz

Chorągiewicz

Turski

et al. 2021

IJMS

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“…OPs are small rhythmic wavelets superimposed on the ascending b-wave of the ERG and STR are negative corneal deflection elicited in the fully dark-adapted eye to dim stimuli. An International Society for Clinical Electrophysiology of Vision (ISCEV) standardized ERG protocol (Marmor et al, 2009 ) included several tests to measure the function of various retinal cell types, including the rod response, standard rod-cone response, Hi-intensity rods, and cones response, cone response, Hi-intensity cone response, flicker, and Hi flicker (Grillo et al, 2018 ). A visualization of nine ERG signals resulting from two ERG components (OP and STR) and seven ERG test responses is provided in Figure 2 .…”

Section: Methodsmentioning

confidence: 99%

“…A visualization of nine ERG signals resulting from two ERG components (OP and STR) and seven ERG test responses is provided in Figure 2 . The dynamics of ERG signals vary in people with various conditions and can therefore aid in differentiating individuals with glaucoma (Grillo et al, 2018 ), schizophrenia (Demmin et al, 2018 ), obesity (Yapici et al, 2021 ), and bipolar disorder (Hébert et al, 2020 ). ERG can also help in evaluating the effectiveness of new or existing drugs and therapy modalities (Lai et al, 2006 , 2009 ; Nebbioso et al, 2009 ; da Silva et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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Novel Machine-Learning Based Framework Using Electroretinography Data for the Detection of Early-Stage Glaucoma

et al. 2022

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PurposeEarly-stage glaucoma diagnosis has been a challenging problem in ophthalmology. The current state-of-the-art glaucoma diagnosis techniques do not completely leverage the functional measures' such as electroretinogram's immense potential; instead, focus is on structural measures like optical coherence tomography. The current study aims to take a foundational step toward the development of a novel and reliable predictive framework for early detection of glaucoma using machine-learning-based algorithm capable of leveraging medically relevant information that ERG signals contain.MethodsERG signals from 60 eyes of DBA/2 mice were grouped for binary classification based on age. The signals were also grouped based on intraocular pressure (IOP) for multiclass classification. Statistical and wavelet-based features were engineered and extracted. Important predictors (ERG tests and features) were determined, and the performance of five machine learning-based methods were evaluated.ResultsRandom forest (bagged trees) ensemble classifier provided the best performance in both binary and multiclass classification of ERG signals. An accuracy of 91.7 and 80% was achieved for binary and multiclass classification, respectively, suggesting that machine-learning-based models can detect subtle changes in ERG signals if trained using advanced features such as those based on wavelet analyses.ConclusionsThe present study describes a novel, machine-learning-based method to analyze ERG signals providing additional information that may be used to detect early-stage glaucoma. Based on promising performance metrics obtained using the proposed machine-learning-based framework leveraging an established ERG data set, we conclude that the novel framework allows for detection of functional deficits of early/various stages of glaucoma in mice.

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Adenosine receptor expression in the adult zebrafish retina

Grillo

McDevitt

Voas

et al. 2019

Purinergic Signalling

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Adenosine is an endogenous nucleoside in the central nervous system that acts on adenosine receptors. These are G proteincoupled receptors that have four known subtypes: A1, A2A, A2B, and A3 receptors. In the present study, we aimed to map the location of the adenosine receptor subtypes in adult wild-type zebrafish retina using in situ hybridization and immunohistochemistry. A1R, A2AR, and A2BR mRNA were detected in the ganglion cell layer (GCL), the inner nuclear layer (INL), the outer nuclear layer (ONL), and the outer segment (OS). A3R mRNA was detected in the GCL, ONL, and OS. A1R-immunoreactivity was expressed as puncta in the INL and in the outer plexiform layer (OPL). A1Rs were located within the cone pedicle and contiguous to horizontal cell tips in the OPL. A2AR-immunoreactivity was expressed as puncta in the GCL, inner plexiform layer (IPL), INL, and outer retina. A2AR puncta in the outer retina were situated around the ellipsoids and nuclei of cones, and weakly around the rod nuclei. A1Rs and A2ARs were clustered around ON cone bipolar cell terminals and present in the OFF lamina of the INL but were not expressed on mixed rod/cone response bipolar cell terminals. A2BR-immunoreactivity was mainly localized to the Müller cells, while A3Rs were found to be expressed in retinal ganglion cells of the GCL, INL, ONL, and OS. In summary, all four adenosine receptor subtypes were localized in the zebrafish retina and are in agreement with expression patterns shown in retinas from other species.

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Quantification of Changes in Visual Function During Disease Development in a Mouse Model of Pigmentary Glaucoma

Abstract: Our data suggest that RGC function as well as interactions of RGCs with other retinal cell types is impaired during glaucoma. In addition, a later OP wavelet denoted as OP4 in this study was identified as a very reproducible indicator of loss of visual function in the glaucoma mouse model.

Cited by 12 publications

References 51 publications

Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma

Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma

Novel Machine-Learning Based Framework Using Electroretinography Data for the Detection of Early-Stage Glaucoma

Adenosine receptor expression in the adult zebrafish retina

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