Aqueous Humor TGF-ß2 and Its Association With Intraocular Pressure in a Naturally Occurring Large Animal Model of Glaucoma.

Purpose: Transforming growth factor (TGF)-ß2 has been widely implicated in human glaucoma pathology. The purpose of this study was to determine the source of TGF-ß2 in aqueous humor (AH) and its relationship with intraocular pressure (IOP) in an inherited large animal model of glaucoma. Methods: Sixty-six glaucomatous cats homozygous for LTBP2 mutation, and 42 normal cats were studied. IOP was measured weekly by rebound tonometry. AH was collected by anterior chamber paracentesis from each eye under general anesthesia, and serum samples collected from venous blood concurrently. Concentrations of total, active and latent TGF-ß2 in AH and serum samples were measured by quantitative sandwich immunoassay. For comparisons between groups, unpaired t-test or Mann Whitney test were used, with P < 0.05 considered significant. The relationships between TGF-ß2 concentrations and IOP values were examined by Pearson's correlation coefficient and generalized estimating equation. Results: IOP and AH TGF-ß2 concentrations were significantly higher in glaucomatous than in normal cats. AH TGF-ß2 showed a significant, robust positive correlation with IOP in glaucomatous cats (r = 0.83, R2 = 0.70, P < 0.0001). Serum TGF-ß2 did not correlate with AH TGF-ß2 and was not significantly different between groups. TGF-ß2 mRNA and protein expression were significantly increased in local ocular tissues in glaucomatous cats. Conclusions: Enhanced, local ocular production of TGF-ß2 with a robust positive association with IOP was identified in this spontaneous feline glaucoma model, providing a foundation for preclinical testing of novel therapeutics to limit disease-associated AH TGF-ß2 elevation and signaling in glaucoma.

Comparison of the TONOVET Plus®, TonoVet®, and Tono-Pen Vet™ tonometers in normal cats and cats with glaucoma.

OBJECTIVES: To determine the accuracy, precision, and clinical applicability of the ICare® TONOVET Plus (TVP) in cats. ANIMALS AND PROCEDURES: IOP readings obtained with the TVP were compared to values obtained concurrently with the original TONOVET (TV01) and Tono-Pen Vet™ (TP) in 12 normal cats (24 eyes) and 8 glaucomatous LTBP2-mutant cats (13 eyes) in vivo. Reproducibility of TVP readings was also assessed for three observers in the above cats. The anterior chambers of five different normal cat eyes were cannulated ex vivo. IOP was measured with the TVP, TV01, and TP at manometric IOPs ranging from 5 to 70 mmHg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. ANOVA was used to assess reproducibility of TVP readings obtained by different observers and an ANCOVA model controlled for variation of individual cats. p < .05 was considered significant. RESULTS: TVP values strongly correlated with TV01 values (y = 1.045x + 1.443, R2 = .9667). The TP significantly underestimated IOP relative to the TVP and TV01, particularly at high IOP. IOP values obtained by 1 observer were significantly higher (~1 mmHg average) compared to the other 2 observers via ANCOVA analysis (p = .0006479 and p = .0203). Relative to manometry, the TVP and TV01 were significantly more accurate (p < .0001) and precise (p < .0070) than the TP in ex vivo eyes. CONCLUSIONS: IOP readings obtained with the TVP and TV01 are broadly interchangeable between models and between observers, but subtle differences may be important in a research context. TP readings vastly underestimate high IOP in feline glaucoma.

From Drugs to Dry Mouth: A Systematic Review Exploring Oral and Psychological Health Conditions Associated with Dry Mouth in Older Adults with Polypharmacy.

BACKGROUND: Approximately 60% of older adults complain of dry mouth, which may be associated with polypharmacy, common in this population. Existing studies have reported treatment approaches to dry mouth but do not address long-term preventative measures that would more positively benefit the health and well-being of older adults. OBJECTIVE: We aimed to explore the consequences of dry mouth, associated with polypharmacy, on the physical and psychological health of older adults in order to establish the importance of preventing dry mouth. METHODS: This systematic review was conducted of studies reporting health conditions of dry mouth, in relation to polypharmacy in older adults (aged ≥ 65 years). MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched using keywords such as 'polypharmacy', 'dry mouth', 'oral health' and 'quality of life' (PROSPERO: CRD42021288945). Joanna Briggs Institute critical appraisal tools were used to assess study quality. RESULTS: Of the 6852 citations screened, nine studies (cross-sectional, n = 8; longitudinal, n = 1) were included that comprised 37,459 participants (mean age range 68.5-85.0 years). Studies were published between 2005 and 2019. Because of the heterogeneity of reported study outcomes, a narrative synthesis was undertaken. The health conditions identified in this review were categorised as 'physical' or 'psychological'. The main physical health conditions reported in the studies related to dental health, such as tooth loss, and functional impairments, such as swallowing difficulties. An increase in the number of medicines taken, from 0 to 5, decreased the number of natural teeth remaining from 16 (standard deviation [SD] ± 9) to 12 (SD ± 8), respectively. Additionally, the number of dental complications increased from 1 (SD ± 2) to 2 (SD ± 2) as the number of medicines increased from 1 to ≥ 3. There was a paucity of studies (n = 2) that investigated psychological health conditions of dry mouth among older adults, with depression identified as a significant issue among older adults with dry mouth (where the reported prevalence was as high as 64%). An additional six psychological health conditions were identified: self-consciousness, feeling tense, difficulty relaxing, irritability, difficulty completing tasks and feeling less satisfied in life. CONCLUSIONS: High levels of physical health conditions of dry mouth are observed in older adults and, to a lesser extent, psychological health conditions. These conditions can negatively affect quality of life. There remains a need to prevent dry mouth and the adverse health conditions associated with it in older adults. The modifiable nature of polypharmacy could be targeted to minimise, and potentially prevent, dry mouth. The optimisation of medication regimes to effectively treat chronic conditions, but also limit the likelihood of dry mouth, is a practical approach. Dry mouth prevention should be a priority and polypharmacy can pave the way for prevention strategies, avoiding the need to treat dry mouth.

Exploring the feasibility of a cluster pilot randomised control trial to improve children's 24-hour movement behaviours and dietary intake: Happy homework.

We aimed to explore the feasibility, acceptability, and potential efficacy of Happy Homework (HH); an 8-week home-focussed intervention, with the purpose of encouraging children's positive dietary behaviours and engagement in positive physical activity (PA) and sleep behaviours. We randomised four Scottish schools (n = 71 participants; 5 classrooms) to either the HH intervention (n = 2) or usual curriculum control group (n = 2). HH consisted of movement and dietary-focused parent and child tasks. Primary outcome measures were intervention feasibility, acceptability, and potential efficacy. Secondary outcomes were objectively measured PA via ActiGraph GT3X+, sedentary behaviours (SBs) and sleep duration via activPAL4™ accelerometers and dietary behaviours, fruit and vegetable consumption and screen-time via questionnaires. After controlling for pre-test levels, post intervention stepping time and sleep duration were significantly greater for the HH group in comparison to the control group. The HH group reported eating more fruit and vegetables at post-test than the control group. Participants also reported the intervention to be enjoyable and motivating. These findings provide promising evidence that given a greater sample size, better retention and the prioritisation of health and wellbeing homework, HH could enhance children's health and wellbeing.

Association between oral health markers and decline in muscle strength and physical performance in later life: longitudinal analyses of two prospective cohorts from the UK and the USA.

BACKGROUND: Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life. METHODS: We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors. FINDINGS: In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]). INTERPRETATION: Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life. FUNDING: The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research.

Outer retinal thickness and visibility of the choriocapillaris in four distinct retinal regions imaged with spectral domain optical coherence tomography in dogs and cats.

PURPOSE: To evaluate the outer retinal band thickness and choriocapillaris (CC) visibility in four distinct retinal regions in dogs and cats imaged with spectral domain optical coherence tomography (SD-OCT). To attempt delineation of a fovea-like region in canine and feline SD-OCT scans, aided by the identification of outer retinal thickness differences between retinal regions. METHODS: Spectralis® HRA + OCT SD-OCT scans from healthy, anesthetized dogs (n = 10) and cats (n = 12) were analyzed. Scanlines on which the CC was identifiable were counted and CC visibility was scored. Outer nuclear layer (ONL) thickness and the distances from external limiting membrane (ELM) to retinal pigment epithelium/Bruch's membrane complex (RPE/BM) and ELM to CC were measured in the area centralis (AC), a visually identified fovea-like region, and in regions superior and inferior to the optic nerve head (ONH). Measurements were analyzed using a multilevel regression. RESULTS: The CC was visible in over 90% of scanlines from dogs and cats. The ONL was consistently thinnest in the fovea-like region. The outer retina (ELM-RPE and ELM-CC) was thickest within the AC compared with superior and inferior to the ONH in dogs and cats (p < .001 for all comparisons). CONCLUSIONS: The CC appears a valid, albeit less than ideal outer retinal boundary marker in tapetal species. The AC can be objectively differentiated from the surrounding retina on SD-OCT images of dogs and cats; a fovea-like region was identified in dogs and its presence was suggested in cats. These findings allow targeted imaging and image evaluation of these regions of retinal specialization.

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.

Relationship Between Parent and Child Physical Activity Using Novel Acceleration Metrics.

Background: Raw acceleration data lend themselves to innovative metrics in which comparisons can be made across populations. This study examined whether the intensity gradient (IG) or average acceleration (AvAcc) was associated with body mass index (BMI) in children and adults and explored parent-child associations between time spent in physical activity intensities and BMI. Methods: Parent-child dyads (n = 90) wore a wrist-mounted ActiGraph GT3X+ monitor for ≥ 3 valid days (i.e., ≥ 16 hrs each day). Participants' BMI was calculated. Results: Girls' BMI-z scores were positively associated with parent BMI and inactive time. Parent BMI was negatively associated with boys' inactive time. Parental inactive time predicted girls' BMI-z scores. The metrics were not associated with parent BMI, and no independent effects were observed between the metrics. Associations between boys' IG and BMI z-score were observed. No independent effects were observed between the metrics and no significant associations were observed between boys' BMI z-score and AvAcc. Girls' AvAcc and IG were not associated with BMI z-score and no independent effects were observed between the metrics. Conclusion: Findings support previous research which suggests that parent's activity does not influence their child's activity.

Development and validation of methods to visualize conventional aqueous outflow pathways in canine primary angle closure glaucoma.

PURPOSE: Angle closure glaucoma (PACG) is highly prevalent in dogs and is often refractory to medical therapy. We hypothesized that pathology affecting the post-trabecular conventional aqueous outflow pathway contributes to persistent intraocular pressure (IOP) elevation in dogs with PACG. The goal of this study was to determine the potential for aqueous angiography (AA) and optical coherence tomography (OCT) to identify abnormalities in post-trabecular aqueous outflow pathways in canine PACG. METHODS: AA and anterior segment OCT (Spectralis HRA + OCT) were performed ex vivo in 19 enucleated canine eyes (10 normal eyes and 9 irreversibly blind eyes from canine patients enucleated for management of refractory PACG). Eyes were cannulated and maintained at physiologic IOP (10-20 mmHg) prior to intracameral infusion of fluorescent tracer. OCT scleral line scans were acquired in regions of high and low perilimbal AA signal. Eyes were then perfusion fixed and cryosections prepared from 10/10 normal and 7/9 PACG eyes and immunolabeled for a vascular endothelial marker. RESULTS: Normal canine eyes showed segmental, circumferential limbal AA signal, whereas PACG eyes showed minimal or no AA signal. AA signal correlated with scleral lumens on OCT in normal dogs, but lumens were generally absent or flattened in PACG eyes. Collapsed vascular profiles were identified in tissue sections from PACG eyes, including those in which no lumens were identified on AA and OCT. CONCLUSIONS: In canine eyes with PACG, distal aqueous outflow channels are not identifiable by AA, despite normalization of their IOP, and intra-scleral vascular profiles are collapsed on OCT and histopathology.

Feasibility and Acceptability of a Classroom-Based Active Breaks Intervention for 8-12-Year-Old Children.

Purpose: This study explored the feasibility of conducting a classroom-based active breaks intervention on sedentary behavior (SB), physical activity (PA) and attention in 8-12-year-old children. Methods: Eight schools were randomized on a 1:1 basis to the control or intervention. Teachers selected 10 cards detailing an activity break at random. Children then undertook each of the ten activity breaks for 30 s, three times per day for 6 weeks. School and participant recruitment, attrition rates, percentage of outcome measures collected, and acceptability were used to explore the feasibility of the study. Mixed effects models were undertaken to examine intervention effects upon measures of PA, SB and attention. Results: Two hundred and thirty-nine consent forms were issued and 153 were returned (64%). Of the 153 consents, 146 children (95%) were measured at baseline, and 117 participated in the follow-up measures (80%) 6 weeks later suggesting the intervention was acceptable for the participants. From teacher interviews, it was noted that the intervention was feasible to implement, and teachers observed positive classroom behavior changes in children. Inclusion rates for outcome measures ranged from 49% to 66%. Significant, intervention effects were observed for sitting time (B = -27.19; 95%CI: -36.84, -17.17), standing time (B = 23.51; 95%CI 14.1, 32.45) and the number of sit to stand transitions (B = 16.1; 95%CI 4.7, 26.79). Conclusion: Findings suggest that it was feasible and acceptable to implement an active breaks intervention within the classroom setting. Future work should consider the effectiveness of implementing this intervention across a full academic year.

The Effects of Socioeconomic Status on Parent and Child Moderate-to-Vigorous Physical Activity and Body Mass Index.

Purpose: Physical inactivity and overweight status has been linked to low socioeconomic status (SES) in youth. Parents are known to influence both their child's weight and physical activity (PA). The relationship between parent and child PA is of interest to many researchers; however, previous research typically relies on self-reported measures. The purpose of this study was to examine the relationship between parent and child moderate-to-vigorous PA (MVPA) and body mass index (BMI) in a sample of children (4-11 years old) using wrist-worn accelerometers and to explore mediating processes by which SES influences child MVPA and BMI through their parents MVPA and BMI. Methods: Parent and child dyads (n = 174) wore an ActiGraph GT3X+ accelerometer on their non-dominant wrist for 7 days. Mediation analyses were conducted to understand the indirect relationships between SES and child MVPA and BMI. Results: Weekend parent and child MVPA was significantly related (p < .01). Parent and child BMIs were also significantly related (p < .001). There was a significant negative direct effect of SES on child BMI (p < .05). Additionally, we observed a significant negative indirect effect of SES on child BMI via their parents BMI (B = -.04, SE .02, 95% CI = -.07 to -.01). Conclusions: Whilst parent and child MVPA were significantly related during the weekend, there were no associations between SES and MVPA. Future interventions aiming to improve health outcomes in children should consider the influence SES can have as well as parental activity on children's weekend MVPA.

Mapping retinal ganglion cell somas in a large-eyed glaucoma model.

Purpose: The purpose of this study was to identify a robust, representative region of interest (ROI) for studies of retinal ganglion cell (RGC) soma loss in feline congenital glaucoma (FCG), a spontaneous, large-eyed glaucoma model. Methods: Seven FCG and three wild-type (wt) eyes were collected from 10 adult cats of both sexes. Eyes enucleated postmortem were immediately fixed overnight in 4% paraformaldehyde and then stored in 0.1 M PBS at 4 °C. The retinas were wholemounted, Nissl stained with cresyl violet, and imaged using light microscopy. Somas of RGCs were manually identified according to long-established morphological criteria and quantified using a semiautomated method; their coordinates were used to create density maps and plots of the retinal topography. The RGC axon counts for the corresponding eyes were obtained from glutaraldehyde-fixed, resin-embedded optic nerve cross-sections stained with 0.1% p-phenylenediamine (PPD) using a semiautomated counting method. Correlations between total optic nerve axons and RGC soma counts were assessed by linear regression. A k-means cluster algorithm was used to identify a retinal ROI, with further definition using a probability density algorithm. Results: Interindividual variability in RGC total soma counts was more pronounced in FCG cats (mean = 83,244, range: 0-155,074) than in wt cats (mean = 117,045, range: 97,373-132,972). In general, RGC soma counts were lower in FCG cats than they were in wt cats. RGC axon counts in the optic nerve cross-sections were lower than, but strongly correlated to, the total RGC soma count across all cats (in wt and FCG retinas; R2 = 0.88) and solely FCG eyes (R2 = 0.92). The k-means cluster algorithm indicated a region of the greatest mean difference between the normal wt retinas and FCG-affected retinas within the temporal retina, incorporating the region of the area centralis. Conclusions: As in other species, RGC soma count and topography are heterogeneous between individual cats, but we identified an ROI in the temporal retina for future studies of RGC soma loss or preservation in a large-eyed model of congenital glaucoma. Many of the methods refined and established to facilitate studies in this FCG model will be broadly applicable to studies in other large-eyed models.

Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models.

Purpose: To characterize the visual pathway integrity of five glaucoma animal models using diffusion tensor imaging (DTI). Methods: Two experimentally induced and three genetically determined models of glaucoma were evaluated. For inducible models, chronic IOP elevation was achieved via intracameral injection of microbeads or laser photocoagulation of the trabecular meshwork in adult rodent eyes. For genetic models, the DBA/2J mouse model of pigmentary glaucoma, the LTBP2 mutant feline model of congenital glaucoma, and the transgenic TBK1 mouse model of normotensive glaucoma were compared with their respective genetically matched healthy controls. DTI parameters, including fractional anisotropy, axial diffusivity, and radial diffusivity, were evaluated along the optic nerve and optic tract. Results: Significantly elevated IOP relative to controls was observed in each animal model except for the transgenic TBK1 mice. Significantly lower fractional anisotropy and higher radial diffusivity were observed along the visual pathways of the microbead- and laser-induced rodent models, the DBA/2J mice, and the LTBP2-mutant cats compared with their respective healthy controls. The DBA/2J mice also exhibited lower axial diffusivity, which was not observed in the other models examined. No apparent DTI change was observed in the transgenic TBK1 mice compared with controls. Conclusions: Chronic IOP elevation was accompanied by decreased fractional anisotropy and increased radial diffusivity along the optic nerve or optic tract, suggestive of disrupted microstructural integrity in both inducible and genetic glaucoma animal models. The effects on axial diffusivity differed between models, indicating that this DTI metric may represent different aspects of pathological changes over time and with severity.

Hypoxic-ischemic injury causes functional and structural neurovascular degeneration in the juvenile mouse retina.

Ischemic stroke is a major cause of long-term disabilities, including vision loss. Neuronal and blood vessel maturation can affect the susceptibility of and outcome after ischemic stroke. Although we recently reported that exposure of neonatal mice to hypoxia-ischemia (HI) severely compromises the integrity of the retinal neurovasculature, it is not known whether juvenile mice are similarly impacted. Here we examined the effect of HI injury in juvenile mice on retinal structure and function, in particular the susceptibility of retinal neurons and blood vessels to HI damage. Our studies demonstrated that the retina suffered from functional and structural injuries, including reduced b-wave, thinning of the inner retinal layers, macroglial remodeling, and deterioration of the vasculature. The degeneration of the retinal vasculature associated with HI resulted in a significant decrease in the numbers of pericytes and endothelial cells as well as an increase in capillary loss. Taken together, these findings suggest a need for juveniles suffering from ischemic stroke to be monitored for changes in retinal functional and structural integrity. Thus, there is an emergent need for developing therapeutic approaches to prevent and reverse retinal neurovascular dysfunction with exposure to ischemic stroke.

Validation and comparison of four handheld tonometers in normal ex vivo canine eyes.

OBJECTIVES: To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer and the Tono-Pen AVIA Vet™ applanation tonometer for intraocular pressure (IOP) measurement in normal ex vivo canine eyes and comparison to earlier models of these tonometers. ANIMALS & PROCEDURES: The anterior chambers of six normal dog eyes were cannulated ex vivo. IOP was measured with the TONOVET (TV01), TONOVET Plus, Tono-Pen Vet™, and Tono-Pen AVIA Vet™ at manometric IOPs ranging from 5 to 70 mm Hg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. A P value ≤ .05 was considered significant. RESULTS: Intraocular pressure values obtained using the TONOVET Plus and TV01 were significantly more accurate than with the Tono-Pen VET and Tono-Pen AVIA Vet, particularly at higher IOPs (30-70 mm Hg). Accuracy was not significantly different between any of the devices in the low to normal physiologic IOP range (5-25 mm Hg). Level of precision was high for all devices, though the TONOVET Plus was more precise than the Tono-Pen Vet in the 5-25 mmHg range and the TV01 was more precise than the Tono-Pen AVIA Vet over the whole IOP range. CONCLUSIONS: All devices underestimated IOP, particularly at higher pressures. Rebound tonometers were more accurate over the full range of IOP tested and in the high IOP range; however, there were no significant differences in accuracy among devices in the physiologic IOP range. All tonometers can provide clinically useful IOP readings in dogs, but rebound and applanation tonometers should not be used interchangeably.

Prophylactic anti-glaucoma therapy in dogs with primary glaucoma: A practitioner survey of current medical protocols.

AIM: To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians. METHODS: A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection. RESULTS: Responses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months. CONCLUSIONS: Data analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.

Microstructure and resident cell-types of the feline optic nerve head resemble that of humans.

The lamina cribrosa (LC) region of the optic nerve head (ONH) is considered a primary site for glaucomatous damage. In humans, biology of this region reflects complex interactions between retinal ganglion cell (RGC) axons and other resident ONH cell-types including astrocytes, lamina cribrosa cells, microglia and oligodendrocytes, as well as ONH microvasculature and collagenous LC beams. However, species differences in the microanatomy of this region could profoundly impact efforts to model glaucoma pathobiology in a research setting. In this study, we characterized resident cell-types, ECM composition and ultrastructure in relation to microanatomy of the ONH in adult domestic cats (Felis catus). Longitudinal and transverse cryosections of ONH tissues were immunolabeled with astrocyte, microglia/macrophage, oligodendrocyte, LC cell and vascular endothelial cell markers. Collagen fiber structure of the LC was visualized by second harmonic generation (SHG) with multiphoton microscopy. Fibrous astrocytes form glial fibrillary acidic protein (GFAP)-positive glial columns in the pre-laminar region, and cover the collagenous plates of the LC region in lamellae oriented perpendicular to the axons. GFAP-negative and alpha-smooth muscle actin-positive LC cells were identified in the feline ONH. IBA-1 positive immune cells and von Willebrand factor-positive blood vessel endothelial cells are also identifiable throughout the feline ONH. As in humans, myelination commences with a population of oligodendrocytes in the retro-laminar region of the feline ONH. Transmission electron microscopy confirmed the presence of capillaries and LC cells that extend thin processes in the core of the collagenous LC beams. In conclusion, the feline ONH closely recapitulates the complexity of the ONH of humans and non-human primates, with diverse ONH cell-types and a robust collagenous LC, within the beams of which, LC cells and capillaries reside. Thus, studies in a feline inherited glaucoma model have the potential to play a key role in enhancing our understanding of ONH cellular and molecular processes in glaucomatous optic neuropathy.