CLN diseases are mostly fatal lysosomal storage diseases that lead to neurodegeneration in the CNS. We have previously shown that CD8+ T-lymphocytes contribute to axonal perturbation and neuron loss in the CNS of Ppt1(-/-) mice, a model of CLN1 disease. We now investigated the role of the inflammation-related cell adhesion molecule sialoadhesin (Sn) in Ppt1(-/-) and Cln3(-/-) mice, a model of the most frequent form, CLN3 disease. Microglia/macrophages in the CNS of both models showed an upregulation of Sn and markers for proinflammatory M1 polarization and antigen presentation. Sn+ microglia/macrophages associated with SMI32+ axonal spheroids and CD8+ T-lymphocytes. To analyze their pathogenic impact, we crossbred both models with Sn-deficient mice and scored axonal degeneration and neuronal integrity using immunohistochemistry, electron microscopy and optical coherence tomography. Degenerative alterations in the retinotectal pathway of Ppt1(-/-)Sn(-/-) and Cln3(-/-)Sn(-/-) mice were significantly reduced. Ppt1(-/-)Sn(-/-) mice also showed a substantially improved clinical phenotype and extended lifespan, attenuated numbers of M1-polarized microglia/macrophages and reduced expression levels of proinflammatory cytokines. This was accompanied by an increased frequency of CD8+CD122+ T-lymphocytes in the CNS of Ppt1(-/-)Sn(-/-) mice, the regulatory phenotype of which was demonstrated by impaired survival of CD8+CD122- effector T-lymphocytes in co-culture experiments. We show for the first time that increased Sn expression on microglia/macrophages contributes to neural perturbation in two distinct models of CLN disease. Our data also indicate that a rarely described CD8+CD122+ T-cell population can regulate the corresponding diseases. These studies provide insights into CLN pathogenesis and may guide in designing immuno-regulatory treatment strategies.

Upregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for ‘Time after stimulation’ (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.

PURPOSE. Insufficient accommodative response is assumed to result in myopia progression. We have investigated if the accommodative lag in myopes is different between a single vision lens (SVL) and the progressive addition lens PAL 2, clinically trialled for its ability to reduce progression of myopia, and if there exist differences in accommodative lag between PAL 2 and other PALs with the same addition power (þ1.50 D).METHODS. The influence of spherical SVL and four different designs of PALs that differ in the near zone width (PAL 1) or that have different signs and magnitude of horizontal gradients of mean power adjacent to their near vision zones (PAL 3 and PAL 4) on the accommodative response was investigated for different near viewing distances (40, 33, and 25 cm) in 31 subjects, aged 18 to 25 years. RESULTS.The SVL correction resulted in insufficient accommodative response for the near object viewing distances tested. PAL 2 did significantly reduce accommodative lag for all near object distances tested. The PAL design with a more negative horizontal mean power gradient (PAL 4) provided a lower lag of accommodation when compared with PAL 2 at the shortest object distance of 25 cm (P ¼ 0.03) and was able to reduce the lag of accommodation to a level below the depth of focus for the higher near working distances tested.CONCLUSIONS. Designs of PAL with more negative horizontal mean power gradients are the most effective in lowering the lag of accommodation in myopes. This could make them good test candidates for myopia control applications.

Since contrast sensitivity (CS) relies on the accuracy of stimulus presentation, the reliability of the psychophysical procedure and observer's attention, the measurement of the CS-function is critical and therefore, a useful threshold contrast measurement was developed. The Tuebingen Contrast Sensitivity Test (TueCST) includes an adaptive staircase procedure and a 16-bit gray-level resolution. In order to validate the CS measurements with the TueCST, measurements were compared with existing tests by inter-test repeatability, testretest reliability and time. The novel design enables an accurate presentation of the spatial frequency and higher precision, inter-test repeatability and test-retest reliability compared to other existing tests. 429-441 (1946). 4. P. G. J. Barten, "Contrast sensitivity of the human eye and its effects on image quality," (SPIE press, 1999), p. 1. 5. M. S. Banks and P. Salapatek, "Acuity and contrast sensitivity in 1-, 2-, and 3-month-old human infants," Invest.Ophthalmol. Vis. Sci. 17(4), 361-365 (1978). 6. R. Hess and G. Woo, "Vision through cataracts," Invest. Ophthalmol. Vis. Sci. 17(5), 428-435 (1978). 7. D. B. Elliott, J. Gilchrist, and D. Whitaker, "Contrast sensitivity and glare sensitivity changes with three types of cataract morphology: are these techniques necessary in a clinical evaluation of cataract?" Ophthalmic Physiol. Opt. 9(1), 25-30 (1989). 8. D. D. Koch, "Glare and contrast sensitivity testing in cataract patients," J. Cataract Refract. Surg. 15(2), 158-164 (1989). 9. G. B. Arden and J. J. Jacobson, "A simple grating test for contrast sensitivity: preliminary results indicate value in screening for glaucoma," Invest. Ophthalmol. Vis. Sci. 17(1), 23-32 (1978).

Altered retinal dopamine and ON-pathway activity may underlie myopia development. It has been shown that the stimulation of the blind spot with short-wavelength light increases the electroretinogram (ERG) b-wave amplitude of myopic eyes and may engage the retinal dopaminergic system. This study evaluated the impact of various durations of blind spot stimulation on the electrophysiological response of the myopic retina and their relationship to axial length. Six myopic individuals underwent three short-wavelength blue light blind spot stimulation protocols (10 s, 1 min, 10 min) using a virtual reality headset. As a control condition, no stimulation was shown for 1 min. The b-wave amplitude of the photopic full-field ERG was measured at baseline and 10, 20, 30, 40, 50, and 60 min after each condition. A significant increase in b-wave amplitude was observed for all stimulation protocols compared to the control. The peak b-wave amplitude was observed 20 min after the 1-min stimulation protocol and 60 min after the 10-min stimulation protocol. A significant positive correlation was found between axial length of the eye and percent change in b-wave amplitude for the 10-min stimulation protocol. A rapid and a delayed b-wave time course responses were observed following 1 min and 10 min of blind spot stimulation, respectively. Overall, these results indicate that light stimulation of the blind spot for various durations elevates ON-bipolar cell activity in the retina and as such is assumed to reduce the myopic response. These findings could have implications for future myopia treatment.