Changes In Eye Growth Research Articles

The choroid-sclera interface: An ultrastructural study

Emmetropization is an active and visually guided process that involves the retina, choroid and sclera, and results in compensatory changes in eye growth. This guided growth is the result of visual cues and possibly mechanical interactions being translated into growth signals via molecular events from the retina into the choroid and sclera, through the choroidal scleral transition zone. If mechanical interactions were a part of the choroid-sclera signaling transduction cascade, specific morphological arrangements should be detectable in this region at the ultrastructural level. The goal of this study was to investigate the ultrastructural features of the choroidal scleral transition zone by comparing avian, non-human primate and human eyes, with the goal to confirm whether specific mechanical structures are present. Choroidal and scleral tissue from chicken, marmoset, and human eyes were imaged using transmission electron microscopy to document the choroid-sclera transition zone. In chicken eyes, fibroblast lamellae bordered the scleral matrix and formed thin end elongated processes that were undercut by scleral collagen fibrils. These processes back-looped into the scleral matrix, and displayed small club-like membrane protrusions. Differences in these arrangements in mature vs young chickens were not detected. The club-like membrane protrusions identified in chickens were rare in marmoset eyes, which instead exhibited two types of collagen fibrils discriminated by size, and were absent in the human eyes investigated. In marmoset and human eyes, elastic components were detected in the transition zone that were absent in chickens. In summary, cellular/membrane specializations indicating a mechanical interaction at the choroid-sclera transition zone were not detected in chicken, non-human primate or human eyes. If mechanotransduction is necessary for scleral growth, matrix integrity or development, alternative structural arrangements might be required.

Electroretinography and Gene Expression Measures Implicate Phototransduction and Metabolic Shifts in Chick Myopia and Hyperopia Models.

The Retinal Ion-Driven Fluid Efflux (RIDE) model theorizes that phototransduction-driven changes in trans-retinal ion and fluid transport underlie the development of myopia (short-sightedness). In support of this model, previous functional studies have identified the attenuation of outer retinal contributions to the global flash electroretinogram (gfERG) following weeks of myopia induction in chicks, while discovery-driven transcriptome studies have identified changes to the expression of ATP-driven ion transport and mitochondrial metabolism genes in the retina/RPE/choroid at the mid- to late-induction time-points. Less is known about the early time-points despite biometric analyses demonstrating changes in eye growth by 3 h in the chick lens defocus model. Thus, the present study compared gfERG and transcriptome profiles between 3 h and 3 days of negative lens-induced myopia and positive lens-induced hyperopia in chicks. Photoreceptor (a-wave and d-wave) and bipolar (b-wave and late-stage d-wave) cell responses were suppressed following negative lens-wear, particularly at the 3–4 h and 3-day time-points when active shifts in the rate of ocular growth were expected. Transcriptome measures revealed the up-regulation of oxidative phosphorylation genes following 6 h of negative lens-wear, concordant with previous reports at 2 days in this model. Signal transduction pathways, with core genes involved in glutamate and G-protein coupled receptor signalling, were down-regulated at 6 h. These findings contribute to a growing body of evidence for the dysregulation of phototransduction and mitochondrial metabolism in animal models of myopia.

Influence of the time of day on axial length and choroidal thickness changes to hyperopic and myopic defocus in human eyes

Research in animal models have shown that exposing the eye to positive or negative spectacle lenses can lead to predictable changes in eye growth. Recent research indicates that brief periods (1–2 h) of monocular defocus results in small, but significant changes in axial length and choroidal thickness of human subjects. However, the effects of the time of day on these ocular changes with defocus are not known. In this study, we examined the effects of monocular myopic and hyperopic defocus on axial length and choroidal thickness when applied in the morning (change between 10 a.m. and 12 p.m.) vs the evening (change between 5 and 7 p.m.) in young adult human participants (mean age, 23.44 ± 4.52 years). A series of axial length (using an IOL Master) and choroidal thickness (using an optical coherence tomographer) measurements were obtained over three consecutive days in both eyes. Day 1 (no defocus) examined the baseline ocular measurements in the morning (10 a.m. and 12 p.m.) and in the evening (5 and 7 p.m.), day 2 investigated the effects of hyperopic and myopic defocus on ocular parameters in the morning (subjects wore a spectacle lens with +3 or −3 DS over the right eye and a plano lens over the left eye between 10 a.m. and 12 p.m.), and day 3 examined the effects of defocus in the evening (+3 or −3 DS spectacle lens over the right eye between 5 and 7 p.m.). Exposure to myopic defocus caused a significant reduction in axial length and thickening of the subfoveal choroid at both times; but, compared to baseline data from day 1, the relative change in axial length (−0.021 ± 0.009 vs +0.004 ± 0.003 mm, p = 0.009) and choroidal thickness (+0.027 ± 0.006 vs +0.007 ± 0.006 mm, p = 0.011) with defocus were significantly greater for evening exposure to defocus than for the morning session. On the contrary, introduction of hyperopic defocus resulted in a significant increase in axial length when given in the morning (+0.026 ± 0.006 mm), but not in the evening (+0.001 ± 0.003 mm) (p = 0.047). Furthermore, hyperopic defocus resulted in a significant thinning of the choroid (p = 0.005), but there was no significant influence of the time of day on choroidal changes associated with hyperopic defocus (p = 0.672). Exposure to hyperopic and myopic defocus at different times of the day was also associated with changes in the parafoveal regions of the choroid (measured across 1.5 mm nasal and temporal choroidal regions on either side of the fovea). Our results show that ocular response to optical defocus varies significantly depending on the time of day in human subjects. These findings represent a potential interaction between the signal associated with the eye's natural diurnal rhythm and the visual signal associated with the optical defocus, making the eye perhaps more responsive to hyperopic defocus (or ‘go’ signal) in the morning, and to myopic defocus (or ‘stop’ signal) in the latter half of the day.

Lag of accommodation does not predict changes in eye growth in chickens

Emmetropization is controlled by the defocus in the retinal image. It is a classical problem how changes in focus, introduced by accommodation, are taken into account. We have quantified accommodation errors in chickens wearing negative lenses to find out whether they can predict subsequent eye growth. Two groups of chicks, aged 10 to 13 days, wore lenses (−7D) monocularly for 4–7 days. Fellow eyes remained untreated. Vitreous chamber depth (VCD) was measured in alert hand-held chickens with high resolution, using the Lenstar LS 900 (Haag-Streit, Koeniz, Switzerland). Non-cycloplegic refractive state was measured by automated infrared photoretinoscopy with and without the lenses in place. In group 1 (n = 6), measurements were done 5 times a day to obtain detailed VCD growth curves. In group 2 (n = 10), measurements were only taken twice, at 9 am and 4 pm, to reduce the risk of recovery from induced myopia due to the frequent removal of the lenses. As expected from the negative power of the lenses, refractions measured through the lenses were more hyperopic although not as much as predicted by the lens powers, indicating that chickens partially refocused their eyes by accommodation. Among different animals, accommodation errors varied from 1.1 ± 0.9 to 3.6 ± 1.1D (group 1, mean ± 1 standard deviation) and 0.22 ± 1.25 to 1.72 ± 1.23D (group 2). No correlations were found between the magnitude of the accommodation errors in individual animals and subsequent changes in VCD. With negative lenses, VCD grew both during day and night while fellow eyes grew only during the day but shrank during the night. In conclusion, accommodation errors did not predict future eye growth. This raises the question as to why brief periods of clear vision, when lenses are taken off, have a strong inhibitory effect on myopia development while periods of clear vision due to accommodation have apparently no effect. A possible explanation is that, in addition to retina-driven control of eye growth, there is a second neural pathway for the control of eye growth that carries the signal of accommodation – although it is striking that no neuronal and structural correlate has been identified to date.

Daily morning light therapy is associated with an increase in choroidal thickness in healthy young adults

Ambient light exposure is one environmental factor thought to play a role in the regulation of eye growth and refractive error development, and choroidal thickness changes have also been linked to longer term changes in eye growth. Therefore in this study we aimed to examine the influence of a 1-week period of morning light therapy upon choroidal thickness. Twenty two healthy young adult subjects had a series of macular choroidal thickness measurements collected with spectral domain optical coherence tomography before, and then following a 7-day period of increased daily light exposure. Increased light exposure was delivered through the use of commercially available light therapy glasses, worn for 30 minutes in the morning each day. A significant increase in subfoveal choroidal thickness (mean increase of +5.4 ± 10.3 µm) was found following 7-days of increased daily light exposure (p = 0.02). An increase in choroidal thickness was also observed associated with light therapy across the central 5 mm macular region. This study provides the first evidence in the human eye that daily morning light therapy results in small magnitude but statistically significant increases in choroidal thickness. These changes may have implications for our understanding of the impact of environmental factors upon eye growth.

Imposed anisometropia, accommodation, and regulation of refractive state.

To determine the effects of imposed anisometropic retinal defocus on accommodation, ocular growth, and refractive state changes in marmosets. Marmosets were raised with extended-wear soft contact lenses for an average duration of 10 weeks beginning at an average age of 76 d. Experimental animals wore either a positive or negative power contact lens over one eye and a plano lens or no lens over the other. Another group wore binocular lenses of equal magnitude but opposite sign. Untreated marmosets served as controls and three wore plano lenses monocularly. Cycloplegic refractive state, corneal curvature, and vitreous chamber depth were measured before, during, and after the period of lens wear. To investigate the accommodative response, the effective refractive state was measured through each anisometropic condition at varying accommodative stimuli positions using an infrared refractometer. Eye growth and refractive state are significantly correlated with the sign and power of the contact lens worn. The eyes of marmosets reared with monocular negative power lenses had longer vitreous chambers and were myopic relative to contralateral control eyes (p < 0.01). Monocular positive power lenses produced a significant reduction in vitreous chamber depth and hyperopia relative to the contralateral control eyes (p < 0.05). In marmosets reared binocularly with lenses of opposite sign, we found larger interocular differences in vitreous chamber depths and refractive state (p < 0.001). Accommodation influences the defocus experienced through the lenses, however, the mean effective refractive state was still hyperopia in the negative-lens-treated eyes and myopia in the positive-lens-treated eyes. Imposed anisometropia effectively alters marmoset eye growth and refractive state to compensate for the imposed defocus. The response to imposed hyperopia is larger and faster than the response to imposed myopia. The pattern of accommodation under imposed anisometropia produces effective refractive states that are consistent with the changes in eye growth and refractive state observed.

Astigmatism Associated with Experimentally Induced Myopia or Hyperopia in Chickens

Astigmatism is a very common refractive error in humans, but its etiology is poorly understood. The primary purpose of this study was to determine whether alterations in visual experience would result in astigmatism in chicks. Longitudinal and cross-sectional data were obtained from chicks that were raised undergoing four different visual manipulations known to alter axial eye growth: form deprivation by translucent occluders, spherical defocus by -10- or +10-D lenses, and constant light. The visual manipulations began at 5 days of age and continued for a week. Age-matched groups raised without any treatment or with Velcro rings or plano lenses served as control groups. Refractions in all birds were measured with a Hartinger refractometer, and infrared photokeratometry was performed in a subset of birds at the end of the treatment period. In control birds, natural astigmatism decreased in magnitude over the 7-day treatment period. In contrast, birds treated with visual manipulations developed significant amounts of astigmatism throughout the treatment period. At the end of the 7-day treatment period, whereas only 8.6% of the control chicks had refractive astigmatism >1 D, the percentage of treated birds that had astigmatism >1 D in each treatment group ranged from 66.7% to 100%. The astigmatism in the treated eyes was predominantly against-the-rule, corneal in nature, and correlated significantly with spherical ametropia of the principal meridians. Visual manipulations known to induce axial ametropia also promote the genesis of astigmatism in chickens. The characteristics of astigmatism associated with spherical myopia or hyperopia in chicks is similar to those reported in humans in many respects, supporting the hypothesis that vision-dependent changes in eye growth may contribute to the astigmatism commonly found in humans.

Glucagon Receptor Agonists and Antagonists Affect the Growth of the Chick Eye: A Role for Glucagonergic Regulation of Emmetropization?

In chicks, plus defocus retards eye growth, thickens the choroid, and activates glucagonergic amacrine cells, probably releasing glucagon. Glucagon receptor antagonists (expected to inhibit compensation to plus defocus) and agonists (expected to block myopia induction by form deprivation) were administered to eyes of chicks, to test the hypothesis that glucagon mediates the induction of changes in eye growth by plus defocus. Seven-day-old (P7) chick eyes were injected intravitreally with peptides at concentrations of approximately 10(-9) to 10(-5) M in 20 microL (injection volume). The glucagon-receptor antagonists [des-His(1),des- Phe(6),Glu(9)]-glucagon-NH(2) (des- Phe(6)-antagonist) and [des-His(1),Glu(9)]-glucagon-NH(2) (Phe(6)-antagonist) were administered daily for 4 to 5 days to plus-defocused eyes. Agonists (porcine glucagon-[1-29] and [Lys(17,18),Glu(21)]-glucagon-NH(2)) were monocularly administered daily for 5 days to form-deprived eyes. The contralateral eye remained open and received saline. After treatment, eyes were refracted, measured, and examined for histologic changes. The Phe(6)-antagonist at 10(-5) M (in the syringe) inhibited changes in both refractive error and axial length compensation induced by +7-D lens wear; however, des-Phe(6)-antagonist (10(-5) M) had weak, inconsistent effects and did not antagonize the action of exogenous glucagon. Glucagon prevented ocular elongation and myopia and induced choroidal thickening in form-deprived eyes. [Lys(17,18),Glu(21)]-glucagon-NH(2) had little effect at 10(-7) M, but at 10(-6) to 10(-5) M altered rod structure and inhibited eye growth. Exogenous glucagon inhibited the growth of form-deprived eyes, whereas Phe(6)-antagonist inhibited compensation to plus defocus, as might be expected if glucagon is an endogenous mediator of emmetropization. The reason for the failure of des-Phe(6)-antagonist to counteract the effects of exogenous glucagon requires further investigation.

The role of the retinal pigment epithelium in eye growth regulation and myopia: A review

Myopia is increasing in prevalence world-wide, nearing epidemic proportions in some populations. This has led to expanded research efforts to understand how ocular growth and refractive errors are regulated. Eye growth is sensitive to visual experience, and is altered by both form deprivation and optical defocus. In these cases, the primary targets of growth regulation are the choroidal and scleral layers of the eye that demarcate the boundary of the posterior vitreous chamber. Of significance to this review are observations of local growth modulation that imply that the neural retina itself must be the source of growth-regulating signals. Thus the retinal pigment epithelium (RPE), interposed between the retina and the choroid, is likely to play a critical role in relaying retinal growth signals to the choroid and sclera. This review describes the ion transporters and signal receptors found in the chick RPE and their possible roles in visually driven changes in eye growth. We focus on the effects of four signaling molecules, otherwise implicated in eye growth changes (dopamine, acetylcholine, vasoactive intestinal peptide (VIP), and glucagon), on RPE physiology, including fluid transport. A model for RPE-mediated growth regulation is proposed.

Astigmatism in monkeys with experimentally induced myopia or hyperopia.

Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 +/- 0.33 D [control] vs. 1.24 +/- 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson's r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. In infant monkeys, visual conditions that alter axial growth can also alter corneal shape. Similarities between the astigmatic errors in our monkeys and some astigmatic errors in humans suggest that vision-dependent changes in eye growth may contribute to astigmatism in humans.

Model of retinal surface area and neuron distribution in the avian eye

Changes in retinal neuron distribution may reflect normal or pathological changes in retinal function. The quantitative study of retinal neurons provides a better understanding of anomalous mechanisms, such as those controlling ocular growth and refractive error development in experimental animals. We developed a method to facilitate the quantitative analysis of amacrine neuron populations in wholemount chick retinae, since the domestic chicken is used extensively as an animal model in myopia studies. This method involved automated cell counting from confocal microscopic images and mathematical estimation of total cell numbers based on image cell density and retinal surface areas. Cell densities and cell counts were obtained from immunohistochemically-labeled amacrine neuron populations, using derived formulae to calculate retinal surface area based on vitreous chamber depth, equatorial width, ora serrata diameter and scleral thickness. Normalized total cell counts in each eye were compared, rather than cell densities, since changes in eye growth can affect cell densities. We also compared neuron distribution in central versus peripheral portions of the retina. This is an alternative technique for retinal analysis that supplements traditional anatomical cell counting methods, allowing higher numbers of specimens to be rapidly analyzed.

Compensatory changes in eye growth and refraction induced by daily wear of soft contact lenses in young marmosets

Several studies have shown that growth of the primate eye responds in a compensatory direction to both positive and negative spectacle lenses — eyes grow more slowly and become hyperopic in response to positive lenses, and eyes grow more rapidly and become myopic in response to negative lenses. On the other hand, extended wear soft contact lenses, whether positively or negatively powered, induce hyperopia ( Hung & Smith, 1996. Extended-wear, soft, contact lenses produce hyperopia in young monkeys. Optometry & Vision Science 73, 579–584.). We investigated whether responses in a compensatory direction occurred to soft contact lenses worn on a daily wear basis (8 h per day on an 8:16 h light:dark cycle). Ten infant marmosets (8–13 weeks of age) wore a soft contact lens, in one eye only, for 5–9 weeks. Lens powers used were zero ( n=2), +2D ( n=1), +2D followed after 5 weeks of lens wear by +4D ( n=1) for 4 weeks, +4D ( n=2), −2D followed after 5 weeks of lens wear by −4D ( n=2) for 4 weeks, −4D ( n=2). At the end of the lens-wear period the positive lens-wearing eyes were more hyperopic relative to the fellow untreated eyes [mean +2.39±0.24D (SE)] and the negative lens-wearing eyes were more myopic than the fellow untreated eyes [mean −2.48±0.91D (SE)]. Fellow eyes were unaffected by lens wear [mean final refraction +0.45±0.09D (SE)]. Plano lenses did not affect eye growth in either marmoset fitted with plano contact lenses.

Local changes in eye growth induced by imposed local refractive error despite active accommodation.

We have tested whether defocus imposed on local retinal areas can produce local changes in eye growth, even if accommodation is available to clear part of the imposed defocus. Hemi-field lenses were attached to little leather hoods that were worn by young chickens from day 11-15 post-hatching. The lens segments defocused either the nasal or the temporal visual field, or covered the full field. We found that negative lenses (-7.5 D) were incompletely compensated in all three cases but caused significant myopia in the defocused parts of the visual field (differences to fellow eyes with normal vision: nasal visual field -3.13 +/- 1.56 D, P < 0.001; temporal visual field -4.02 +/- 1.38 D, P < 0.001; full field -3.82 +/- 2.48 D, P = 0.01). Myopia was not enhanced if the lenses covered the entire visual field. Positive lenses (+6.9 D) caused larger changes in refraction than negative lenses and, again, there was no significant difference in the amount of induced hyperopia in the nasal or temporal retina, or in the amount of hyperopia with full-field lenses (difference to fellow eyes with normal vision: nasal visual field +6.2 +/- 2.69 D, P < 0.001; temporal visual field +5.95 +/- 2.22 D, full field +7.22 +/- 2.44 D, P < 0.001). To compare the shapes of the excised eyes after lens treatment, we wrote a fully automated image processing program that traced their outlines in digitized video images. We found that the shapes of the eyes treated with positive lenses did scarcely differ from their fellow eyes with normal vision, indicating that hyperopia over this 4 day period was caused mostly by choroidal thickening. Full field negative lenses produced significant axial eye elongation; the effects of locally imposed defocus on eye shape were less conspicuous and were significant only in some areas. That local compensation of defocus was possible for both negative and positive lenses, suggests that the retina can recognize the sign of defocus without accommodation cues. Even more striking is that the presence of accommodation is apparently ignored since the drift in the plane of focus during accommodation does not disturb the compensation process. We re-analyze previous experimental results that argue for different mechanisms for deprivation myopia and lens-induced refractive errors. We propose that lens-induced refractive errors are compensated by similar retinal mechanisms as the ones proposed by Bartmann and Schaeffel [(1994). Vision Research, 34, pp. 873-876] to explain deprivation myopia. The proposed mechanisms can integrate with long time constants over the spatial frequency content in the retinal image while the viewing distances change, and control both choroidal thickening and scleral growth. However, it turns out that the compensation of imposed myopia cannot be explained if only one constant viewing is available. Apparently, there is more than a retinal blur detector to guide refractive development.

Changes in eye growth produced by drugs which affect retinal ON or OFF responses to light.

The interaction between drugs which affect ON and OFF responses to light and ocular growth was investigated in 154 eyes of newly-hatched chicks raised with normal vision or monocular occlusion with regular intravitreal injections of APB (2-amino-4 phosphonobutyric acid) or PDA (cis 2,3-piperidine-dicarboxylic acid). The experimental results indicate that APB, at a dose sufficient to abolish the b-wave of the electroretinogram (but not to show extensive damage to the retinal neurons at the light microscopic level), caused a significant decrease in the axial growth of the eyes when compared with normal eyes. APB did not result in a significant difference in the growth rates of the occluded eyes compared with occluded controls. By contrast, injection of PDA into occluded eyes at a dose which reduced the response at light offset in the electroretinogram (and also affected the ON-response), caused a dramatic reduction in elongation of those eyes compared with occluded controls. Injection of PDA into eyes raised in a normal visual environment did not induce a significant difference from the growth rate of normally reared control eyes. These growth changes support the hypothesis that drugs which affect the physiological function of the retina, in particular, the strength of the ON and OFF responses, interact with the visual rearing environment to cause a consistent pattern of changes to eye growth and refractive error.

Studies on the role of the retinal dopamine/melatonin system in experimental refractive errors in chickens

We have found that development of both deprivation-induced and lens-induced refractive errors in chickens implicates changes of the diurnal growth rhythms in the eye (Fig. 1). Because the major diurnal oscillator in the eye is expressed by the retinal dopamine/melatonin system, effects of drugs were studied that change retinal dopamine and/or serotonin levels. Vehicle-injected and drug-injected eyes treated with either translucent occluders or lenses were compared to focus on visual growth mechanisms. Retinal biogenic amine levels were measured at the end of each experiment by HPLC with electrochemical detection. For reserpine (which was most extensively studied) electroretinograms were recorded to test retinal function [Fig. 3 (C)] and catecholaminergic and serotonergic retinal neurons were observed by immunohistochemical labelling [Fig. 3(D)]. Deprivation myopia was readily altered by a single intravitreal injection of drugs that affected retinal dopamine or serotonin levels; reserpine which depleted both serotonin and dopamine stores blocked deprivation myopia very efficiently [Fig. 3(A)], whereas 5,7-dihydroxy-tryptamine (5,7-DHT), sulpiride, melatonin and Sch23390 could enhance deprivation myopia (Table 1, Fig. 5). In contrast to other procedures that were previously employed to block deprivation myopia (6-OHDA injections or continuous light) and which had no significant effect on lens-induced refractive errors, reserpine also affected lens-induced changes in eye growth. At lower doses, the effect was selective for negative lenses (Fig. 4). We found that the individual retinal dopamine levels were very variable among individuals but were correlated in both eyes of an animal; a similar variability was previously found with regard to deprivation myopia. To test a hypothesis raised by Li, Schaeffel, Kohler and Zrenner [(1992) Visual Neuroscience, 9, 483-492] that individual dopamine levels might determine the susceptibility to deprivation myopia, refractive errors were correlated with dopamine levels in occluded and untreated eyes of monocularly deprived chickens (Fig. 6). The hypothesis was rejected. Although it has been previously found that the static retinal tissue levels of dopamine are not altered by lens treatment, subtle changes in the ratio of DOPAC to dopamine were detected in the present study. The result indicates that retinal dopamine might be implicated also in lens-induced growth changes. Surprisingly, the changes were in the opposite direction for deprivation and negative lenses although both produce myopia. Currently, there is evidence that deprivation-induced and lens-induced refractive errors in chicks are produced by different mechanisms. However, findings (1), (3) and (5) suggest that there may also be common features. Although it has not yet been resolved how both mechanisms merge to produce the appropriate axial eye growth rates, we propose a scheme (Fig. 7).

Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens.

Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.