Circadian IOP Rhythm in Rats Is Driven by Neural Signals From the Brain

Figures

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  Figure 1.. Time dependence of IOP responses to TTX. (A) Representative IOP data from a rat entrained to LD and transitioned to DD. Black and white bars indicate light and dark phases of ECU illumination, and gray shading indicates SN of the animal. (B) IOP responses to TTX instillation at four different times of the circadian cycle (CT3, CT11, CT15, and CT19). Symbols indicate instillation time. (C) IOP response to saline solution instillation at CT15. Symbol indicates instillation time. (D) Summary of IOP data pre- and post- TTX (white and gray columns) for different instillation times. Connected symbols indicate measurements from individual animals (n = 4 per condition). Error bars give standard deviation. Asterisks indicate significance level: *P < 0.05; **P < 0.01.

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  Figure 2.. Dose-dependence of IOP response to TTX. (A) IOP records from a rat in SD during which TTX was applied at 1, 0.1, and 0.01 mg/mL (gray traces). Symbols indicate instillation time. Black trace gives the fit of a difference-of-pulses function to the raw data. (B) Summary of TTX dosage effect across animals. IOP reduction is expressed as a percent of the peak-to-peak rhythm amplitude. Connected symbols indicate measurements from individual animals (n = 3). Asterisks indicate significance level: *P < 0.05.

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  Figure 3.. Dynamics of IOP response to TTX. (A) A 24-hour IOP record from a rat in DD during which TTX was applied midway through SN (black trace). Symbol indicates instillation time. Red trace and dots give a linear fit of TTX onset and offset responses and the times to max-effect (left) and half-recovery (right), respectively. (B) Summary of onset dynamics of IOP lowering by TTX and offset dynamics of the IOP rhythm reduction at subjective dawn (DL). Connected symbols indicate measurements from individual animals (n = 6). n.s., not significant.

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  Figure 4.. Long-term effects of TTX on IOP rhythmicity. (A) Four-day IOP record from a rat in DD during which TTX was applied during one SD. Symbol indicates instillation time. Horizontal lines demark data segments used for cosinor analysis to quantify rhythm properties before and after instillation. (B) Summary of rhythm amplitude, period, phase, and baseline level before and after TTX instillation (white and gray columns). Connected symbols indicate measurements from individual animals (n = 8). n.s., not significant.

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  Figure 5.. Effect of TTX on IOP of bilaterally cannulated animals. (A) IOP traces collected concurrently for several DD days from the OD (black) and OS (red) eye of the same rat. (B) The 24-hour IOP records recorded concurrently from both while TTX was applied only to the OD eye (black). Symbol indicates instillation time. (C) Summary of IOP data before and after (white and gray bars) TTX instillation on the treated (OD + TTX) eye and contralateral control (OS) eye. Connected symbols indicate measurements from individual animals. Asterisks indicate significance level: **P < 0.01; n.s., not significant.

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  Figure 6.. Effect of superior cervical ganglionectomy on IOP rhythmicity. (A) Image of the SCG after retracting carotid vessels. Dashed lines mark incision sites in the sympathetic trunk (STx) and internal- (ICNx) and external- (ECNx) carotid nerves. (B) IOP record from a rat in LD during which SCGx was performed to sever sympathetic input to the eye. Symbol indicates SCGx time. (C) Comparison of IOPs during SD and SN (white and gray columns) after SCGx. Connected symbols indicate measurements from individual animals (n = 5). n.s., not significant.