Ocular accommodation control and adaptive optics. The development of monocular and binocular adaptive optics instrumentation for the study of accommodation and convergence, and study of the monocular accommodative response to rapid changes in dioptric stimuli.

The relationship between accommodation and myopia has been under investigation for many years, and the effort to understand it is ongoing. In this thesis, an introduction to the state of myopia research is given first, with particular reference to studies of accommodation and higher-order ocular aberrations, which feature in the subsequent chapters. Following a brief introduction to the general technique of aberrometry and visual stimulus control using adaptive optics, the development of a monocular adaptive optics instrument for this purpose is described. The instrument is used to vary a dioptric stimulus and record the accommodation response in pilot studies and a detailed experiment, which has also been published elsewhere. It is found, among other things, that accommodation can respond to more than one different input level during its latency period, and that such inputs can be stored until components of the accommodation control system are free to process them. Indications of a minimum halting time for accommodation, of around 0.6 s, are presented. In later chapters, the development and testing of a new, binocular adaptive optics apparatus will be found. As well as binocular aberrometry and adaptive optics control of stimulus aberrations, this instrument displaces images to allow for and stimulate ocular convergence in binocular accommodation experiments. It is the first instrument in the world with its combined functionalities. Finally, the contribution of this thesis is summarised, and further instrumentation development and experiments are put forward for the continuation of this branch of accommodation and myopia research

Processing blur of conflicting stimuli during the latency and onset of accommodation

The accommodative response (AR) to changes in dioptric accommodative stimulus (AS) during the latency period and onset of accommodation was investigated. Participants monocularly observed one period of a square wave in AS, with a 2-D baseline and mean, and amplitude 1 D or 2 D; the period of the square wave ranged from 0.10 s to 1.00 s; both increases and decreases were used for the first step in AS. At periods of 0.30 s and longer, accommodation was found to respond to both levels of the stimulus. Rapid retinal monitoring appeared to be taking place for such stimuli. The amplitudes of peaks in AR did not usually depend on whether a particular level of AS occurred first or second, but for 8/40 conditions, a significant difference was found, with a stronger response when the level of AS occurred second. Null or incorrect responses were also observed in many trials, possibly linked with the natural microfluctuations of accommodation. Minimum response times to the changes in AS were observed, which increased with decreasing period of the AS. The time interval between peaks in the AR decreased with decreasing period of the AS. The findings were consistent with a parallel processing model previously proposed for saccades, where input from a later change in stimulus may enter an element of the control system when that element has finished processing an earlier change. More than one change in stimulus may therefore be passing through the multi-element control system at a time

TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel–Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome1 (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral–facial–digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture

Effect of cooling rate on the composition and chemical heterogeneity of quench-induced grain boundary η-phase precipitates in 7xxx aluminium alloys

The mechanical properties and stress corrosion cracking (SCC) resistance of 7xxx series aluminium alloys are significantly affected by the composition and distribution of precipitates formed during heat treatment. In particular, their quench sensitivity is related to the formation of η-phase precipitates that nucleate heterogeneously on grain boundaries at lower cooling rates after solution treatment, which has been a key factor restricting the gauge of hot rolled plates in the aerospace industry. To better understand the effects of slower cooling rates on the composition of quench-induced grain boundary precipitates (Q-GBPs) found in thick plate 7xxx alloys, plasma focused ion beam and high-resolution scanning transmission electron microscopy were used to obtain accurate composition data. The η-phase Q-GBPs have a complex- branched morphology, which develops higher aspect ratios and secondary arms as the cooling rate is reduced. Only a small change in average composition of Q-GBPs was found with cooling rate; but a large scatter was observed. This is caused by significant Zn/Cu/Al composition gradients developing along their principal growth directions in both AA7050 and AA7085 alloys. This concentration gradient did not reduce significantly after a T76 treatment. Simulations of Q-GBP growth with different cooling rates using a CALPHAD-informed phase-field model, with the η-phase represented by a two-sublattice model, gave results consistent with experimental observations. Chemical gradients were predicted to develop in the Q-GBPs due to the changing local equilibrium at the growth front during the cooling. The influence of this non-homogeneous microchemistry on the SCC behaviour of 7xxx alloys is briefly discussed