Optometry and Vision Sciences - Research Publications

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    Hypercapnia Impairs Vascular Responses to Changes in Ocular Perfusion Pressure in Rat Retina
    Cull, G ; Wang, L ; Bui, BV (Association for Research in Vision and Ophthalmology, 2018-07-01)
    Purpose : Retinal vascular resistance is constantly regulated by both myogenic and metabolic mechanisms. While most studies have investigated these mechanisms separately, how they interact to impact the vascular resistance is unclear. We considered whether hypercapnia (HC) modified the effect of ocular perfusion pressure (OPP) lowering, induced by lowering blood pressure (BP) or increasing intraocular pressure (IOP) on retinal vessel diameter (Ø). Methods : In pentobarbital anesthetized Brown Norway rats, breathing ~30% O2 air, normocapnia (NC) and hypercapnia (HC) were achieved by controlled ventilation. A gradual decrease in OPP, at the same rate for BP lowering or IOP elevation, was induced by drawing blood (1ml/min) from a femoral artery or by increasing the IOP manometrically from 10 to 70 mmHg (9.78 mmHg/min) in two subgroups for each NC (BP=7, IOP=9) and HC (BP=9, IOP=5). Arterial CO2 partial pressure (pCO2) was measured. In all groups, image sequences centered on the optic nerve were acquired with a confocal scanning laser ophthalmoscope (cSLO) every 1.5 minutes until OPP was < 20 mmHg. Arteries and veins at 1-disc diameter from optic nerve were analyzed. Change in Ø (%) was normalized to its own baseline (before pressure manipulation) and differences between NC and HC groups were compared. Results : Average pCO2levelwas 35 ±5 mmHg (n=12) in NC and 77 ±18 mmHg (n=10) in HC (p<0.001), and pO2 was >80 mmHg for all animals. In the NC group, lowering BP induced progressive arterial and venous dilation (P<0.0001 and 0.005, respectively. Fig 1); increasing IOP caused vasodilatation in arteries (P<0.0001), but not in veins (P>0.05, Fig 2). Vasodilation was evident when OPP dropped to 50-60 mmHg for both BP and IOP modification. During HC, IOP and BP induced arterial vasodilation was significantly attenuated and venous diameter showed greater compression (P<0.0001 both, 2-way ANOVA) compared to the NC groups. Conclusions : Carbon dioxide levels significantly modifies the capacity for retinal blood vessel to cope with reduction in OPP. This data show that the metabolic status of the retina profoundly impact vascular autoregulation, which has implication for metabolic diseases. This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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    Response of the trilaminar retinal vessel network to intraocular pressure elevation in rat eyes
    Bui, BV ; Zhao, D ; Wang, L ; Fortune, B ; He, Z (Association for Research in Vision and Ophthalmology, 2018-07-01)
    Purpose : It is known that inner retinal blood flow is autoregulated to compensate for changes in ocular perfusion pressure (OPP). However, studies have focused on the superficial vessels. Here we test the hypothesis that the superficial, intermediate and deep retinal vascular plexus show different responses to intraocular pressure (IOP) elevation. Methods : Anesthetized (60:5mg/kg ketamine:xylazine) adult Long Evans rats (n=14) were imaged using optical coherence tomography angiography (OCTA) at baseline (IOP 10mmHg) and in follow up mode to examine the vasculature during IOP elevation (10mmHg steps to 110mmHg, each lasting 3 min). We imaged a 20 x 10-degree field starting at one disc diameter from the optic disc margin. Capillary area (i.e. diameter) within a 2D projection image was determined (% region of interest) for three layers based on segmentation of the structural OCT: superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DVP). Increases and decreases in this parameter can be interpreted as functional “vasodilation” and “vasoconstriction”, respectively, of the column of blood flowing above threshold. Comparisons were made between layers (2-way repeated measures ANOVA, layer vs IOP) following normalisation to baseline (% relative to 10mmHg). Results : Group mean arterial blood pressure at baseline was 125±5 mmHg, thus for the IOPs examined OPP spanned 115±5 to -9±4 mmHg. For OPPs from 115±5 to 77±4 mmHg capillaries within the DCP (9±8%, p<0.05) and ICP (11±10%, p<0.05) showed significant “vasodilation”, whereas those in the SVC showed constriction (-14±6%, p<0.05). For OPPs between 63±4 and 38±4 mmHg, capillary diameter was maintained, by for OPPs below 38mmHg, all layers showed linear attenuation. Significant compression in tissue thickness (retinal nerve fibre, ganglion cell and inner plexiform layers and total retinal thickness) for the same regions were not found until OPP fell below 38mmHg. Conclusions : These data show that the intermediate and deep vascular plexus in the rat retina have a greater capacity for autoregulation against IOP elevation. This might reflect a redistribution of blood flow to the deeper layers during stress. This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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    Reversibility of retinal ganglion cell dysfunction due to chronic IOP elevation.
    Zhao, D ; Wong, VHY ; He, Z ; Nguyen, CTO ; Jobling, AI ; Fletcher, E ; Chinnery, H ; Jusuf, P ; Lim, JKH ; Vingrys, AJ ; Bui, BV (Association for Research in Vision and Ophthalmology, 2018-07-01)
    Purpose : To determine the duration of chronic IOP elevation beyond which ganglion cell function can no longer recover using the mouse circumlimbal suture model. Methods : IOP elevation was induced in anaesthetized (isoflurane) adult male C57BL6/J mice by attaching a circumlimbal suture (nylon, 10/0) around the equator of one eye, with the contralateral eye serving as a control. The suture was left in place for 8, 12 and 16 weeks (n=27, 23 and 27), respectively, and animals underwent electroretinography and optical coherence tomography at these time points. In two other groups, the suture was removed after 8 and 12 weeks (n=26 and 28), and the capacity for recovery assessed 4 weeks later. IOP was measured weekly (Tonolab). Retinal ganglion cell (RGC) function (or integrity) was assessed with the positive scotopic threshold response (pSTR) and retinal nerve fibre layer (RNFL) thickness. Data (mean ± SEM) were compared using t-test (control vs. treatment) and one-way ANOVA (within groups). Results : IOP in sutured eyes was higher than control eyes (8wk: 17.1 ± 0.3 vs. 26.8 ± 0.6 mmHg, 12wk: 13.8 ± 0.3 vs. 19.5 ± 0.5 mmHg, 16wk: 17.1 ± 0.2 vs. 27.4 ± 0.6 mmHg; all P<0.001). After suture removal, IOP returned to levels comparable to control eyes (8+4wk: 16.9 ± 0.3 vs. 16.1 ± 0.3 mmHg; P=0.08, 12+4wk: 17.3 ± 0.2 vs. 17.1 ± 0.3 mmHg; P=0.5). With IOP elevation, RGC function declined to 75% ± 8% (8wk), 78% ± 7% (12wk) and 59% ± 4% (16wk, all P<0.001) of control eyes. RNFL thinning was also evident (8wk: 84% ± 4%, 12wk: 83% ± 5%; 16wk: 83% ± 3%; P<0.001) but no change in total retinal thickness was noted (P=0.33). Suture removal at week 8 facilitated full recovery of RGC function (97% ± 7%, P=0.9 vs. baseline) 4 weeks later. However, there was no recovery in RNFL thickness (87% ± 3%, P<0.001 vs. baseline). When the suture was removed at week 12, neither function (79% ± 9%, P<0.05) nor RNFL thickness recovered (89% ± 3%, P<0.01) 4 weeks later. Conclusions : RGC dysfunction can be recovered 4 weeks after an 8-week period of mild IOP elevation, but not after a 12-week period. Beyond 12 weeks, IOP reversal only served to prevent further functional decline. This identifies a critical chronic IOP duration that results in irreversible ganglion cell dysfunction. This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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    Posterior Cerebral Artery Infarct with Haemorrhagic Transformation
    Cham, K ; Wang, J (SciDoc Publishers, 2017)