Parasympathetic influences on emmetropization in chicks: evidence for different mechanisms in form deprivation vs negative lens-induced myopia

Abstract

Ciliary ganglionectomy inhibits the development of myopia in chicks (Schmid et al., 1999), but has no effect on the compensatory responses to spectacle lenses (Schmid and Wildsoet, 1996). This study was done to assess the potential influence of the other parasympathetic input to the choroid, the pterygopalatine ganglia, on the choroidal and axial responses to retinal defocus, and to form deprivation. 4-5 week-old chicks had one of the following surgeries to one eye: (1) Section (X) of the autonomic part of cranial N VII (input to the pterygopalatine ganglia) (PPGX, n = 16), (2) PPGX plus ciliary ganglionectomy (PPG/CGX, n = 23) or (3) PPGX plus superior cervical ganglionectomy (PPG/SCGX, n = 10). Experimental eyes were fitted with positive or negative lenses, or diffusers, several days after surgery. In one group of PPG/CGX, eyes did not wear any devices (n = 8). Intact (no surgery) controls were done for all visual manipulations (lenses or diffusers). Sham surgeries were done for the PPG/CGX condition (n = 4). Ocular dimensions were measured using A-scan ultrasonography prior to the surgery, 5 days later when visual devices were placed on the eyes, at the end of lens- or diffuser-wear, and in the case of diffusers, 4 days after diffuser removal to look at "recovery". Refractive errors were measured using a Hartinger's refractometer. IOP was measured in 7 PPG/CGX birds 7d after surgery. PPGX/CGX resulted in choroidal thickening (125 μm) and a decrease in IOP over one week post-surgery. It also prevented the development of myopia in response to form deprivation (X vs intact: 0.2 D vs -4.1 D; p < 0.005), by preventing the increase in axial elongation (250 μm vs 670 μm/5d; p < 0.005). In fact, growth rate slowed below normal (X vs fellow eyes: 250 μm vs 489 μm/5d; p = 0.002). By contrast, there were no effects of this lesion on the development of myopia in response to negative lenses (X vs intact: -5.4 D vs -5.3 D). All three lesions inhibited the compensatory choroidal thickening in response to myopic defocus (ANOVA, p = 0.0008), but had no effect on the thinning response to hyperopic defocus. These results argue for different underlying mechanisms for the growth responses to form deprivation vs negative lens wear. They also imply that choroidal thickening and thinning are not opposing elements of a single mechanism.

Figure 1

Time line for ultrasound measurements (arrows and arrowheads) for each visual manipulation (left), and numbers for each surgical condition (right). The first measurement was at day 0 for all groups; this was immediately prior to the surgery. 5 days later, devices were affixed to one eye (“on”) after ultrasound was done. This period is referred to as “pre” in the Tables, and reflects effects on eyes prior to the visual manipulation. “Off” (arrowheads) is when the devices were removed, and the eyes remeasured. In the case of the form deprivation group (FD), eyes were allowed to “recover” for 4 days following diffuser removal, at which time they were re-measured.

Figure 2

Effects of lesions on eyes over the 5 days prior to the wearing of visual devices; black bars are experimental eyes, white bars are fellow controls. “Sham” are data for PPG/CGX sham-operated controls. A. Mean change in choroidal thickness for each group over 5 days after surgery. B. Top: Effect of PPG/CGX as a function of time on choroids in eyes without lenses (n=8). Bottom. Effect of PPG/CGX on IOP following the surgery. Day 0 is immediately prior to surgery. C. Mean change in anterior chamber depth; same conventions as in A. D. Mean change in axial elongation; same conventions as in A. Error bars are standard errors of the mean in all graphs. *p<0.05, **p<0.005, ***p<0.0005

Figure 3

Effects of lesions on eyes wearing diffusers (form deprivation) over the course of 5 days. “Intact” refers to form deprived eyes without surgery. A. End refractive errors for all groups in diopters (D). “Fellow” are the combined fellow eye data from all groups, in all graphs. B. Histogram showing numbers of eyes for all refractive errors (D) for the PPG/CGX birds for lesioned eyes (black bars), fellow controls (white bars), and intact controls (striped bars). Note that the refractions for the lesioned eyes completely overlap with those of the fellow eyes. C. Change in axial length (μm/5d) in paired experimental (black bars) and fellow (white bars) eyes. D. Change in axial length for individual experimental (black bars) and fellow (white bars) eyes for all 5 birds in the PPG/CGX condition. E. Change in choroidal thickness. *p<0.05, **p<0.005

Figure 4

Effects of lesions on eyes “recovering” from form deprivation myopia over the course of 4 days. “Intact” refers to “recovering” eyes without surgery. A. Change in axial length (μm/4d). B Change in axial length (left) and final eye size (right) for individual experimental (black bars) and fellow (white bars) eyes for all 5 birds in the PPG/CGX condition. C. Change in choroidal thickness. **p<0.005

Figure 5

Effects of lesions on eyes wearing negative lenses. Intact” refers to negative lens-wearing eyes without surgery. A. End refractive error for all groups (D). B. Change in axial length (μm/5d) for paired experimental (black bars) and fellow control (white bars) eyes. C. Change in choroidal thickness. *p<0.05

Figure 6

Effects of lesions on eyes wearing positive lenses. “Intact” refers to positive lens-wearing eyes without surgery. A. End refractive error for all groups (D). B. Change in axial length (μm/3d) for paired experimental (black bars) and fellow control (white bars) eyes. Note that only the intact and sham groups have significant differences between experimental and fellow eyes. C. Change in choroidal thickness. Black diamond: sham-operated controls. *p<0.05, **p<0.005

Figure 7

Effects of lesions on anterior chamber depth for eyes responding to positive (A) and negative (B) lenses. Black bars: experimental eyes, white bars: fellow controls. “Sham” is the sham-operated PPG/CGX group. There is a trend towards an inhibition in anterior chamber growth for both of the double-lesion conditions in negative lens-wearing eyes. *p<0.05, **p<0.005