Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008

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proliferate after terminal differentiation occurs before birth. As a consequence, there will be no replacement of the cellular loss that occurs later in life. Other neurogenic and myogenic factors include reduced conduction capacity, alteration in neuromuscular transmission, and loss of myofilaments.1,2,3 Furthermore, the discharge frequency in the motor neurons serving all striated muscle fibers is influenced by a number of pre-motor areas in the cortex and brainstem. A progressive decline in neural interaction between these areas will influence the efferent signal to the extraocular muscles, as well as to their somatic counterparts. The co-contraction of extraocular muscles and somatic muscles—which is so essential to maintaining good visual perception during head and body movements—will suffer accordingly. This may, in turn, result in modification of behavior, such as changes in posture, balance, and hand-eye coordination that are commonly observed in elderly patients.4,5

Despite the intimate neural relationship between the somatic motor system and the oculomotor system, the functional principals of the respective systems are fundamentally different in many respects. The constant weight of the eye, along with the absences of a variable external load creates a fixed relationship between the efferent innervation to the extraocular muscles, and the resulting rotation of the eyes.6 This renders the demand for sensory feedback virtually redundant, and suggests that the role of proprioception in oculomotor control is different than in other somatic motor systems. The absence of a stretch reflex in extraocular muscles,7 and the complement of unique sensory receptors, seem to support this notion.8,9 In addition to unique physiological and morphological features, there is also a distinct organization of the distal insertion in these muscles. Human extraocular muscles have complex structures of collagen at their distal insertions that are believed to influence the line of pull of the muscle during eye rotations.10 This organization is inconsistent with the distal insertions of conventional somatic muscles, where tendon attaches directly to bone. These, and other factors addressed below, indicate that our current knowledge of the conventional somatic motor system can not serve as a satisfactory model for understanding the functional implication of age-related changes in the human oculomotor system.

Several studies have documented age-related changes in saccadic velocity, optokinetic nystagmus, and smooth pursuit eye movements.11 Changes in these complex patterns of eye rotation strongly suggest that it is not only the extraocular muscles that are subjected to age-related changes, but also the central control mechanisms responsible for coordination and tuning of the various oculomotor functions. In other words, both the subnuclear and supranuclear level of the oculomotor system seem to be subjected to age-related changes.

Age-related changes can occur simultaneously with pathological changes, and the differentiation between the two conditions can, in some cases, represent a diagnostic challenge. Detailed knowledge of the process of senescence can hence serve as a valuable clinical tool in enhancing the diagnosis and management of a broad spectrum of visual disorders.

This chapter aims to review the most important parameters in oculomotor control, and provide information regarding the functional implications of the agerelated changes taking place in the tissues of the oculomotor system.

common pathway from the nuclei of the three oculorotatory cranial nerves down to the extraocular muscles constitutes the subnuclear level of the oculomotor system.

Age-related Changes in the Supranuclear Level of the Human Oculomotor System

Because age-related changes at the supranuclear level have other clinical manifestations compared to those at the subnuclear level, it is of clinical significance to differentiate between the two.

The term supranuclear embraces all structures and neural activity that have a direct or indirect impact on the discharge frequency in the motor neurons of the III, IV, and VI cranial nerve nuclei. The ability to coordinate the activity in whole muscle groups rather than single muscles makes the supranuclear structures able to execute complex patterns of eye rotations, such as saccadic, optokinetic, vestibular, convergence, and smooth-pursuit eye movements. Age-related changes in the various supranuclear structures can compromise these gaze functions, and factors such as the weight loss that occurs in the brain as we grow older has been argued to be a contributing factor in the development of oculomotor anomalies. The reduction in weight, which represents approximately 8–10 percent between young and old, is attributed to loss of neurons and changes in intracellular content, extracellular volume, and/or reduction in cell processes.4 All of these neurogenic factors could influence the discharge frequency in the oculorotatory nerves and subsequently lead to the development of concomitant deviations. However, because only a minority of mature patients develop concomitant anomalies, there are clearly some adaptive mechanisms that can tune the system and compensate for the neural loss. This would require accurate sensory feedback from the extraocular muscles or other structures participating in ocular dynamics.

One of the supranuclear structures that receive this type of input is the cerebellum. The role of the cerebellum as a coordinator of motor activity is reflected in the large number of ascending fibers in comparison to the rather modest number of fibers descending from it (40:1).

The Cerebellum

The cerebellum has been implicated in a variety of oculomotor functions, and plays an essential role in the long-term adaptive process that compensates for oculomotor dysmetria. This function, which is essential for maintaining oculomotor performance throughout the ageing process,13 relies primarily on the neural input from the vestibular system, the proprioceptive system and specific cerebral cortical areas.

Information from theses sources terminate in different regions of the cerebellar cortex and make it possible to divide the cerebellum into compartments or modules