Biomedical subjects

N A McBrien

Publications and source records attributed to N A McBrien.

At least 19 recordsLinked to original sources

PubMed2001

Inhibition of myopia development in chicks using himbacine: a role for M(4) receptors?

The success of the M(1)-selective muscarinic antagonist pirenzepine in preventing myopia development in animal models implicates a role for the M(1) receptor. However, the relatively high dose of pirenzepine required may indicate that the drug acts through another receptor subtype. This study examined whether the M(4)-selective antagonist, himbacine, could also prevent myopia. Daily intravitreal injections of himbacine inhibited the inducement of myopia in chick eyes in a dose- dependent manner. Doses < or = 200 microg caused no significant inhibition of induced myopia compared to controls (-13.7 +/- 2.3 vs -16.2 +/- 0.9D, ANOVA p = 0.37), whilst a dose of 800 microg almost completely inhibited the induced myopia (-2.4 +/- 2.0, p < 0.01). Findings demonstrate himbacine is effective at preventing the development of myopia in chick and implicates a role for the M4 receptor.

Age Factors↗

PubMed2001

Diisopropylfluorophosphate alters retinal neurotransmitter levels and reduces experimentally-induced myopia.

The excessive enlargement of the eye seen in myopia is known to be regulated, in part, by retinal neurotransmitters. One excitatory retinal neurotransmitter, acetylcholine, has been implicated in the signal cascade through the effectiveness of the muscarinic antagonist, atropine, in preventing myopia development. The present study therefore examined whether an indirect cholinomimetic, diisopropylfluorophosphate (DFP), could increase the level of experimental myopia, induced by the deprivation of pattern vision. Injections of either phosphate-buffered DFP or phosphate-buffered saline were made every 48 h into the vitreous chamber of one eye of chicks. The injected eye was then deprived of pattern vision by a translucent occluder. The fellow eye remained untreated and acted as a genetic control. At the end of the treatment period (8 days) axial ocular dimensions and cycloplegic refractive error were measured. To investigate the effects of DFP on retinal neurotransmitter levels, measurements of acetylcholine and dopamine contents were made on retinal tissue following either a single or multiple DFP injections, using reverse phase high performance liquid chromatography (HPLC). Rather than potentiating myopia and vitreous chamber elongation, a significant reduction in myopia (58%) was observed in DFP-injected deprived eyes, compared to saline controls. However, open eyes injected with DFP showed no difference in refraction or vitreous chamber depth compared to contralateral control eyes or saline controls. HPLC analysis revealed increased steady-state content of acetylcholine (+34 +/- 6 ng/mg protein, mean +/- SEM, P<0.01, equivalent to a 54% increase) and dopamine (+377 +/- 83 pg/mg protein, P<0.01, a 36% increase) in DFP-treated eyes compared to contralateral control eyes following a single DFP injection. No changes in either acetylcholine or dopamine content were found in saline-treated control animals. Injection of dopamine antagonists, in combination with DFP, indicated that the DFP-induced reduction in myopia is mediated, at least in part, through a D2 receptor mechanism. Findings argue against a direct cholinergic 'stop-go' pathway controlling ocular growth. Instead the reduction of induced myopia could be related to the action of DFP (directly or indirectly) on dopamine levels in the retina.

Acetylcholine↗

PubMed2001

Glycosaminoglycan synthesis in the separate layers of the chick sclera during myopic eye growth: comparison with mammals.

PURPOSE: Studies in animal models of refractive development have shown that the development of and recovery from induced myopia is associated with visually-guided changes in scleral glycosaminoglycan synthesis. The present study sought to determine whether differential patterns of scleral glycosaminoglycan synthesis are present in the fibrous scleral layer of the chick during myopia development or recovery, as has previously been reported in the mammalian sclera. METHODS: Myopia was induced in young chicks by monocular deprivation of pattern vision over 5 days. Other animals underwent monocular deprivation, then had the occluder removed and were allowed 2 days of recovery. A group of age-matched normal animals served as a control. Newly synthesised glycosaminoglycans in the scleral layers were labelled in vivo, using a [(35)S]-labelled precursor delivered intraperitoneally on the final experimental day. Incorporation of this sulphate into glycosaminoglycans of the fibrous and cartilaginous scleral layers was assessed in proteinase K digests by selective precipitation with alcian blue. RESULTS: Glycosaminoglycan synthesis in the fibrous scleral layers of myopic and recovering eyes was not significantly different to contralateral control eyes (+14 +/- 7%, p = 0.09 and -2 +/- 4%, p = 0.64 respectively). In contrast, glycosaminoglycan synthesis was significantly elevated, relative to controls, in the cartilaginous scleral layer of eyes developing myopia (+63 +/- 18%, p < 0.02), whereas in recovering eyes there was found to be a significant decrease in synthesis in the cartilaginous layer (-40 +/- 6%, p < 0.001). CONCLUSIONS: The results of the current study demonstrate that the fibrous scleral layer of the chick does not display the characteristic differential patterns of glycosaminoglycan synthesis that are found in the mammalian sclera during myopia development and recovery. However, as has previously been reported, the cartilaginous layer of the chick sclera does display differential glycosaminoglycan expression, although the direction of regulation is opposite to that found in the fibrous sclera of mammals.

Animals↗

PubMed2001

The role of visual information in the control of scleral matrix biology in myopia.

Changes in eye size during the development of refractive error are accompanied by alterations in scleral biochemistry in both humans and animal models of myopia. This review discusses more recent data on scleral changes in mammalian models of myopia and considers the role of visual information in the control of scleral matrix biology. These visually-driven changes in scleral biochemistry are placed in the context of both the emmetropisation process and the abnormal enlargement of the eye that is characteristic of human high myopia.

Animals↗

PubMed2001

High-resolution semi-quantitative real-time PCR without the use of a standard curve.

The repeatability and sensitivity of a simple, adaptable, semi-quantitative, real-time RT-PCR assay was investigated. The assay can be easily and rapidly applied to quantitate relative levels of any gene product without using standards, provided that amplification conditions are specific for the PCR product of interest. Using the LightCycler real-time PCR machine, a serial 10-fold dilution series (spanning four orders of magnitude) of a 379-bp cDNA template was amplified, and the PCR product was detected using SYBR Green I chemistry. The experiment was repeated on a subsequent day. The experimental design was such that the data lent itself to analysis using an appropriate method for testing repeatability. It was found that, within a single assay, for samples assayed in triplicate, a difference of 23% may be reliably detected. Furthermore, when all of the factors that contribute to variability in the assay are taken into account, such as day-to-day variation in pipetting and amplification efficiency, a 52% difference in target template can be detected using a sample size of 4. The assay was found to be linear over at least four orders of magnitude.

Animals↗

PubMed2001

Using diplopia as a warning of an inappropriate visual (ocular) accommodative response (WIVAR).

BACKGROUND: Over-accommodation, a tendency to focus at a distance closer than the desired distance, has been previously shown to occur when using a head-up display (HUD). METHODS: A simple system was developed as a warning of an inappropriate visual accommodative response (WIVAR) during flight training. Two lines, which are seen as four low-contrast lines (physiological diplopia) if the user is focused in the distance due to the link between convergence and accommodation, are projected onto the pilot's HUD combiner. RESULTS: The results show that by using the WIVAR system the accommodative response can be kept more distant when viewing forward-looking infra-red imagery (by 0.12 +/- 0.04 D; p < 0.05), performing a high cognitive workload task (by 0.07 +/- 0.03 D; p < 0.05) and especially when viewing in a Ganzfeld (by 0.41 +/- 0.12 D; p < 0.01). CONCLUSION: While collimated HUD imagery stimulates the user to a more distant focus, the use of the WIVAR lines can cause additional relaxation of accommodation.

Accommodation, Ocular↗

PubMed2001

Structural and ultrastructural changes to the sclera in a mammalian model of high myopia.

PURPOSE: The development of high myopia is associated with scleral thinning and changes in the diameter of scleral collagen fibrils in humans. In the present study, the association between these scleral changes and the losses in scleral tissue that have previously been reported in animal models were investigated to determine the relationship between changes in collagen fibril architecture and thinning of the sclera in high myopia. METHODS: Myopia was induced in young tree shrews by monocular deprivation of pattern vision for short-term (12 days) or long-term (3-20 months) periods. Scleral tissue from normal animals over a wide age range (birth to 21 months) was also collected to provide data on the normal development of the sclera. Light and electron microscopy were used to measure scleral thickness and to determine the frequency distribution of collagen fibril diameters in the sclera. Tissue loss was monitored through measures of scleral dry weight. RESULTS: Significant scleral thinning and tissue loss, particularly at the posterior pole of the eye, were associated with ocular enlargement and myopia development after both short- and long-term treatments. However, collagen fibril diameter distribution was not significantly altered after short-term myopia treatment, whereas, from 3 months of monocular deprivation onward, significant reductions in the median collagen fibril diameter were noted, particularly at the posterior pole. CONCLUSIONS: The results of this study demonstrated that loss of scleral tissue and subsequent scleral thinning occurred rapidly during development of axial myopia. However, this initial tissue loss progressed in a way that did not result in significant alterations to the collagen fibril diameter distribution. In the longer term, there was an increased number of small diameter collagen fibrils in the sclera of highly myopic eyes, which is consistent with findings in humans and is likely to contribute to the weakened biomechanical properties of the sclera that have previously been reported.

Animals↗

PubMed2000

Induced myopia associated with increased scleral creep in chick and tree shrew eyes.

PURPOSE: To investigate the role of scleral creep in the axial elongation of chick and tree shrew eyes with induced myopia. METHODS: Form-deprivation myopia was induced with a diffusing occluder worn over one eye. Scleral samples from the posterior pole and equatorial regions of myopic, contralateral (control), and age-matched normal chick and tree shrew eyes were loaded in vitro with a force of 5 g for 20 minutes while creep extension was monitored. The elastic behavior of sclera from myopic, control, and normal chick eyes was also compared. RESULTS: In both chick and tree shrew, posterior and equatorial scleral samples from myopic eyes had significantly (P < 0.05) greater creep extensions than equivalent samples from control and normal eyes (n = 10, each group). Among individual tree shrews the difference in creep rate between the sample from the myopic eye and that from the control eye correlated with vitreous chamber elongation (r = 0.746, P < 0.05) and development of myopia (r = 0.792, P < 0.01) in the deprived eye. No such association was found in the data from chicks. The elastic properties of chick sclera were unaffected in form-deprivation myopia. CONCLUSIONS: In chick and tree shrew, form-deprivation myopia is associated with increased creep rate of posterior and equatorial sclera. In tree shrew, the correlation between increased scleral creep rate and vitreous chamber elongation in myopic eyes supports the hypothesis that induced changes in the axial length of the mammalian eye are mediated by changes in the creep properties of the sclera.

Animals↗

PubMed2000

Scleral remodeling during the development of and recovery from axial myopia in the tree shrew.

PURPOSE: Recent investigations have suggested that scleral thinning in mammalian eyes with axial myopia is a consequence of the loss of scleral tissue, rather than the redistribution of existing tissue as the eye enlarges. The present study investigated whether further changes in the distribution and metabolism of scleral tissue occur during the process of recovery from axial myopia. Scleral glycosaminoglycan (GAG) synthesis and content as well as scleral dry weight changes were monitored as indicators of remodeling in myopic and recovering tree shrew sclerae. METHODS: Myopia was induced in tree shrews by monocularly depriving them of pattern vision. Some animals then had the occluder removed and were allowed to recover from the induced myopia for periods of 1, 3, 5, 7, and 9 days. Newly synthesized GAGs were radiolabeled in vivo with [(35)S]sulfate. Sulfate incorporation and total GAG content in the sclera was measured through selective precipitation of GAGs from proteinase K digests with alcian blue dye. Dry weights of the sclerae were also determined. Changes in ocular refraction and eye size were monitored using retinoscopy, keratometry, and ultrasonography. RESULTS: Eyes developing myopia showed a significant reduction in scleral GAG synthesis, particularly in the region of the posterior pole (-36% +/- 7%) compared with contralateral control eyes. Scleral dry weight was also significantly reduced in these eyes (-3.7% +/- 1.2%). In recovering eyes, significant changes in GAG synthesis were apparent after 24 hours of recovery. After 3 days of recovery, significantly elevated levels of GAG synthesis were found (+79% +/- 15%), returning to contralateral control eye values after 9 days of recovery. Interocular differences in scleral dry weight were shown to follow a similar pattern to that observed for GAG synthesis. CONCLUSIONS: Active remodeling, resulting in either the loss or replacement of scleral tissue and not passive redistribution of scleral tissue, is associated with changes in eye size during both myopia development and recovery. Regulatory changes in scleral metabolism can be rapidly evoked by a change in visual conditions and the direction of regulation is related to the direction of change in eye size.

Animals↗

PubMed1999

Modulation of scleral DNA synthesis in development of and recovery from induced axial myopia in the tree shrew.

Visually modulated scleral extracellular matrix remodelling is associated with the development of, and recovery from, induced axial myopia in the tree shrew, a commonly used mammalian model of refractive error development. The involvement of scleral cell proliferation in this process was investigated using [3H] thymidine. Tree shrews were monocularly deprived of pattern vision, using translucent occluders, or the retinal image was optically defocused, using negative lenses, over a period of 5 days. A further group was monocularly deprived for 5 days, then allowed 3 days of binocular recovery. A control group of binocularly open animals was employed to establish normal parameters. On the final day of the experimental period, [3H] thymidine was administered by intraperitoneal injection, then optical and biometric measures were taken and tissue samples collected for assay. Incorporation of [3H] thymidine into cellular DNA was measured in proteinase K digests, following precipitation with trichloroacetic acid. After 5 days, significant amounts of myopia were present in the treated eyes of both form-deprived [-7. 0+/-0.7 Dioptres (D), group mean+/-s.e.m.; P<0.01] and lens-defocused animals (-6.2+/-0.9 D;P<0.01). After 3 days of recovery, 50% of the refractive error had been compensated for, predominantly through shortening of the vitreous chamber in the treated eye. Reduced levels of [3H] thymidine incorporation were observed in sclera from both groups of myopic animals (form-deprived, -34.3+/-9.9%;P<0.05 and lens-defocus, -32.8+/-4.5%;P<0.005). Increased levels of [3H] thymidine incorporation were found in the sclera of recovering animals (+144.0+/-43.2%;P<0.05). The results show that changes in regulation of cell proliferation, during the development of myopia, are visually mediated and inversely related to the direction of change in ocular size. This implies that alterations in the scleral fibroblast population are involved in the modulation of scleral matrix turnover during myopia development.

Animals↗

PubMed1999

Optical correction of induced axial myopia in the tree shrew: implications for emmetropization.

PURPOSE: To determine whether an active emmetropization mechanism is involved in the recovery from axial myopia through the use of a mammalian model of refractive development. Specifically, we sought to establish whether the emmetropization mechanism is visually guided by the level of clarity of the image falling on the retina, or if recovery is driven by a mechanism sensitive to abnormal eye shape. METHODS: Young tree shrews had axial myopia induced by monocular deprivation (MD) of pattern vision and then the myopic eye was either: (1) accurately corrected with a negative lens or (2) had a zero-powered lens placed in front of it. Their emmetropization response was monitored, both through the use of ocular refractive and biometric measures, as well as through the assessment of scleral dry weight and glycosaminoglycan synthesis, as indicators of scleral metabolism. RESULTS: Corrective lenses prevented recovery from induced myopia (-6.8 +/- 0.7 D after 5 days MD vs. -6.6 +/- 0.6 D after 5 days of lens wear), whereas animals fitted with zero-powered lenses displayed near full recovery from the induced myopia (-6.6 +/- 0.6 D vs. -1.7 +/- 0.3 D). Significant reductions in scleral dry weight (-4.6 +/- 1.3%) and glycosaminoglycan synthesis (-28.6 +/- 7.3%) were found in the posterior sclera of animals wearing corrective lenses. Conversely, animals wearing zero-powered lenses displayed elevated levels of glycosaminoglycan synthesis (+62.3 +/- 11.1%) in conjunction with scleral dry weights that did not differ significantly between treated and fellow control eyes (-1.5 +/- 2.6%). CONCLUSIONS: Accurate correction of induced axial myopia prevents the refractive, biometric and scleral metabolic responses that are normally observed in tree shrew eyes recovering from induced myopia. These findings support the hypothesis that recovery is driven by an active emmetropization response dependent on the clarity of image falling on the retina and not by a mechanism that is sensitive to abnormal eye shape.

Accommodation, Ocular↗

PubMed1999

Does over-accomodation occur when using aircraft head-up displays?

BACKGROUND: Whether over-accommodation is caused by the use of head-up displays is still under debate. Most prior experimentation has involved cognitively demanding tasks, which are known to affect the accommodation response. The simulations have often been unrealistic and involved short working distances. HYPOTHESIS: Over-accommodation is caused not by the presence of a head-up display per se, but rather by the cognitive demand of the task. METHODS: The effect of increasing the task cognitive load and the use of forward looking infra-red imagery (FLIR) on the ocular accommodative response and task performance was assessed with a realistic head-up display assisted flying task. FLIR increases cognitive load due to its poor resolution and the need for interpretation of the images. RESULTS: Over-accommodation was found to be small in magnitude (0.17+/-0.03D; range -0.02-0.45D) occurring only with cognitively demanding tasks and with forward looking infrared imagery. Response times to detect tanks in the outside world scene were slower with increased cognitive load and forward looking infra-red imagery, along with a reduced detection rate, decreased accuracy of tracking tanks in the outside world and poorer control of the head-up display pitch ladder. When discrimination was added to detection in an outside world task, decisions were delayed until they could be accurately made, rather than performance degraded. CONCLUSION: The use of a virtual head-up display in a simulated aircraft environment did not adversely affect ocular accommodation. However, increased cognitive demand or FLIR imagery caused significant inward shifts of accommodation.

Accommodation, Ocular↗

PubMed1999

Prevention of form-deprivation myopia with pirenzepine: a study of drug delivery and distribution.

The present study investigated the drug distribution and elimination profiles in ocular tissues of pirenzepine, a selective M1 muscarinic antagonist known to inhibit myopia. Results demonstrate that (1) Intravitreal injections of the M1 selective antagonist pirenzepine were more effective at preventing form-deprivation myopia than subconjunctival injections. (2) Maximum drug levels were reached within 1 hr for both retina and sclera following intravitreal (28 and 11 nanomole) and subconjunctival (0.25 and 1 nanomole) injection. Intravitreal injection proved a more effective route of drug delivery to all ocular tissues compared to subconjunctival injection. (3) Elimination times of pirenzepine from ocular tissues were much shorter than those reported for blood plasma. (4) Histological examination revealed no evidence of gross toxic effects at doses effective in inhibiting induced axial myopia. In conclusion, pirenzepine was effective at reducing form-deprivation myopia in a dose-dependent manner with no evidence of disruption to the retina. However, results were not conclusive as to where pirenzepine may have its site of action in preventing form-deprivation myopia.

Animals↗

PubMed1998

The influence of cognition and age on accommodation, detection rate and response times when using a car head-up display (HUD).

Car head-up displays (HUDs), which portray information in the form of a virtual image reflected off a combiner, allow the viewing of complex information, such as route guidance, without the need for the driver to look away from the road ahead. The cognitive demand required by the HUD task may distract drivers from the outside world scene and cause reaction times to slow. Cognitive capacity also decreases with age. The aim of the present study was to determine the effect of cognitive demand and age on the use of a car HUD. Subjects (young, middle or older age drivers, each group n = 8) performed a HUD-assisted driving task, with three levels of cognitive demand, whilst accommodation was simultaneously measured using a dynamically recording infra-red optometer. Response times to, and the detection rate of, changes in both the HUD image and the outside world scene were analysed. Increasing the cognitive demand associated with the HUD image increased over-accommodation (greatest in the young, 0.34 +/- 0.05 D, p < 0.001). Response times to and detection of changes in the HUD image and outside world scene were significantly worse with increased cognitive demand. Response times to and detection of changes in the HUD image and outside world scene also increased with age. The implication of the results with respect to car HUD design and safety are discussed.

Accommodation, Ocular↗

PubMed1997

A longitudinal investigation of adult-onset and adult-progression of myopia in an occupational group. Refractive and biometric findings.

PURPOSE: To investigate the refractive and biometric changes associated with adult-onset and adult-progression of myopia in an occupational group. METHODS: The sample population consisted of 251 clinical microscopists aged 21 to 63 years. Subjects had their refraction and ocular dimensions measured on four occasions during a 2-year period, and a total of 166 subjects (332 eyes) completed the longitudinal aspect of the study. Refraction was measured objectively with a Canon R-1 autorefractor and subjectively by an optometrist using standard procedures. Corneal curvature and axial ocular dimensions were measured with a keratometer and A-scan ultrasonography, respectively. RESULTS: Of eyes emmetropic at the start of the study, a total of 39% underwent a myopic change in refraction greater than 0.37 diopter (D), with a mean change of -0.58 +/- 0.04 D (mean +/- standard error of the mean; n = 37). This was associated with an elongation of the vitreous chamber of 0.26 +/- 0.05 mm (P < 0.01). Eyes emmetropic at the start of the study that did not undergo a refractive change > 0.37 D (n = 58) during the 2-year study period had a mean change in refraction of 0.02 +/- 0.03 D (P = 0.69) associated with a change in vitreous chamber depth of 0.05 +/- 0.02 mm. Changes in corneal curvature, anterior chamber depth, or lens thickness between the initially emmetropic groups were not significant. The median age of onset of myopia in initially emmetropic eyes was 26.3 years. Of eyes that were myopic at the start of the study, 48% progressed further into myopia by 0.37 D or more during the 2-year period. The mean increase in myopia for the "myopia progressor" group was 0.77 +/- 0.03 D (n = 108 eyes) compared to -0.01 +/- 0.02 D (n = 115 eyes; P = 0.49) for myopes who did not undergo a refractive change > 0.37 D during the study period. The only significant difference in ocular component dimension changes during the study period for these two initially myopic groups was elongation of the vitreous chamber depth (0.24 +/- 0.04 mm versus 0.03 +/- 0.03 mm, P < 0.01). The average age of the myopes who progressed further into myopia during the study was 29.3 years. Axial length-corneal radius ratio at the start of the study was not significantly different between initially emmetropic eyes in which adult onset myopia developed or emmetropic eyes that remained refractively stable. The incidence of adult myopia development during a 2-year period in this occupational group was 45%. CONCLUSIONS: The structural cause of adult-onset and adult-progression of myopia is vitreous chamber elongation.

Adult↗

PubMed1996

The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.

PURPOSE: To determine the efficacy of the M1-selective muscarinic antagonist, pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. METHODS: Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either pirenzepine (17.7 mumol; n = 9) or vehicle control (n = 6). Control groups (n = 6) were used to assess the effects of MD, injection regimen, and drug effects. RESULTS: In sham-injected and saline-injected MD tree shrews, 12 days of MD produced-13.2 D +/- 0.8 D and -14.1 D +/- 0.5 D of axial myopia, respectively. In pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only -2.1 D +/- 1.4 D. The significant reduction in myopia in pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm +/- 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm +/- 0.02 mm and 0.29 mm +/- 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. CONCLUSIONS: Findings demonstrate that chronic administration of the M1-selective muscarinic antagonist, pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism.

Accommodation, Ocular↗

PubMed1996

Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew.

PURPOSE: To investigate whether structural changes to the sclera during form-deprivation myopia are caused by active tissue remodeling, the gelatinase activity of tree shrew scleras was studied in normal animals, form-vision deprived animals, and animals recovering from myopia. METHODS: Infant tree shrews were monocularly deprived (MD) of form vision with translucent occluders for 5 days. Recovery animals were allowed 3 days of binocularly unoccluded vision after the period of form deprivation. Eyes were removed and dissected to provide scleral samples corresponding to equatorial and posterior regions. Gelatinase activity was assessed by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE, gelatin, zymography of scleral matrix metalloproteinase (MMP) extracts. RESULTS: The major gelatinolytic species present in tree shrew sclera was found to be MMP-2 (gelatinase A). In normal (nondeprived) animals, most of the MMP-2 was found to be in the latent form (the ratio of active-to-latent MMP-2 was 0.23 +/- 0.05 and 0.34 +/- 0.06 in equatorial and posterior samples, respectively; n = 10 eyes from five animals). After 5 days of MD, there was a threefold increase in the amount of active scleral MMP-2 in myopic eyes compared to contralateral control eyes, whereas latent MMP-2 activity levels were not altered significantly. This increase in active MMP-2 was seen in both the equatorial and posterior sclera of myopic eyes (active-to-latent MMP-2 ratios were 0.53 +/- 0.10 and 0.81 +/- 0.09 in equatorial and posterior regions, respectively; n = 6 animals). Contralateral control eyes had levels of both active and latent MMP-2 not significantly different from normal eyes. After only 3 days of unoccluded vision, previously deprived eyes that were now recovering from myopia had a fivefold lower level of active MMP-2 than that seen in deprived eyes after 5 days of MD. In fact, active (and latent) MMP-2 levels were reduced in recovering eyes even below the levels found in their contralateral control eyes. Active-to-latent ratios for recovering eyes were 0.11 +/- 0.03 and 0.15 +/- 0.03 in equatorial and posterior sclera, respectively (n = 5 animals). CONCLUSIONS: These results demonstrate that form-deprivation myopia and recovery from myopia alter scleral catabolism and provide further support for the theory that changes in eye size during mammalian refractive development are the result of active tissue remodeling rather than passive scleral stretching alone.

Animals↗

PubMed1995

The effects of blockade of retinal cell action potentials on ocular growth, emmetropization and form deprivation myopia in young chicks.

To investigate the influence of brain mediated functions on control of ocular growth, young chicks were treated monocularly with intravitreally injected tetrodotoxin (TTX) to block retinal ganglion cell action potentials. TTX injections (0.7 micrograms in 7 microliters) were given on day 6 after hatching in both binocularly open and monocularly deprived chicks. Injections were repeated every 48 hr for a period of 8 days (TTX-open; TTX-MD). Control groups of animals received intravitreally injected phosphate buffered saline (PBS-open; PBS-MD) to one eye on the same schedule. There was a minimum of eight animals in each group. Recovery from form-deprivation myopia during blockade of retinal cell action potentials was also investigated. Results demonstrate that blockade of retinal cell action potentials by TTX produces reduced growth of the anterior segment of the eye and crystalline lens in both binocularly open and MD chicks. Blockade of retinal cell action potentials does not prevent form-deprivation induced vitreous chamber elongation and myopia. Form deprived myopic eyes were found to emmetropize despite blockade of retinal ganglion cell action potentials giving further evidence for local ocular control of emmetropization. Blockade of retinal ganglion cell action potentials did not prevent changes in choroidal thickness in eyes developing axial myopia or eyes recovering from induced myopia.

Action Potentials↗