本文就視網膜上的視覺級聯轉導反應(visual transduction cascade)和外節膜盤生成與脫落(outer segment disk genesis and shedding) 進行解述，文末附有關鍵詞的中文釋義
The rods and cones are the end organs of vision and are photosensitive. The various layers of the retina are bound together by neuroglia. There are well developed vertical fibers of müller, which have supportive as well as nutritive functions. The internal limiting membrane separate the retinal nerve fiber layer from the vitreous, while the external limiting membrane is perforated by the rods and cones.
The retina converts photons of light to signals describing visual information and sends them to the brain. This process takes place in the outer segments of the photoreceptors, including in the cell membranes and pigment disk membranes of the outer segments.
The steps in the absorption of a photon of light and conversion to useful visual information are called the visual transduction cascade. In the first step, a photon strikes 11-cis-retinal linked to an opsin by a Schiff’s base linkage, converting this retinoid to the all-trans form. This results in subtle shape changes to the opsin that activates the transduction cascade starting first with Transducin.
The opsins are part of the large family of G-protein-coupled receptors, and Transducin is a G-protein. Transducin in turn activates a cGMP-phosphodiesterase (PDE6). This enzyme selectively and specifically converts cGMP to GMP. The cGMP is an allosteric effector of the sodium channel. The drop in levels of cGMP, normally at about 10 μM (in the dark), to about 1 μM (in bright light) changes a Na channel from open to closed. This results in a reduction in the flow of sodium ions and less current flow (known as the Dark Current). In a dose–response manner, the reduced current flow reduces the release of the neurotransmitter glutamate in the photoreceptor synapse.
In the absence of light, the visual transduction cascade can be reset to the dark state. An accumulation of cGMP results from the activity of guanylate cyclase (mediated by GCAPs) that converts GTP to cGMP. This resets the Na channels to their open state restoring the Dark Current. Rhodopsin is restored with 11-cis-retinal. Transducin is restored by the combined actions of RGS9 and recoverin reuniting all the subunits. The PDE6 is reset by combining with a gamma subunit.
首先，光子撞擊11-順-視黃醛，Schiff’s鹼基與視蛋白連接，將順-視黃醛轉化為全反式-視黃醛，激活轉導蛋白引起級聯轉導反應。轉導蛋白反之激活cGMP磷酸二酯酶(PDE6)。PDE6選擇性和特異性地將cGMP轉化為GMP。cGMP是鈉通道的別構效應劑。當cGMP水平從通常的濃度10μM(黑暗中)降至1μM(強光下)時，Na通道由開放變為關閉，鈉離子流動降低(稱為暗電流)，減少光感受器突觸中神經遞質穀氨酸的釋放。黑暗的環境時，在GCAPs的介導下，活化的鳥苷酸環化酶將GTP轉化為cGMP，cGMP不斷累積，使鈉通道再次開放從而恢復暗電流，以重置黑暗下的視覺級聯傳導狀態。
Since phototransduction takes place in the cell membranes and disk membranes of the outer segments of the rods and cones, and the opsins continually need to be replenished, including with Vitamin A provided by the systemic circulation via the choriocapillaris, there is a continual production and shedding of these outer membrane structures. This remarkable process rejuvenates the outer segment structure providing for fresh photosensitive pigments on a continuous basis within the cells.
The tips of outer segments are shed daily and phagocytosed by the RPE cells. The new outer segment disks are generated next to the ciliary process of the photoreceptors. Specifically, the movement of outer segment disks in the outer segment of rods. Daily, a group of about 50~100 new outer segment disks are synthesized at the base of the rod outer segment, and they migrate upward daily, pushed upward by the next new group of disks. Correspondingly, the oldest 50~100 disks (now 10 days old) at the distal tip of the outer segment are phagocytosed by the RPE, resulting in a uniform length of 500~1000 disks per outer segment.
每天約有50~100個新的外節膜盤在視杆細胞底部合成，並不斷向上遷移，推動原來的膜盤向上移動。相應地，位於外節遠端最初的50~100個膜盤(10天前合成)被RPE吞噬，使每個外節維持在500~1000個膜盤的一致長度。
rods and cones 視杆細胞和視錐細胞
photons 光子
outer segments of the photoreceptors 光感受器外節
cell membranes 細胞膜
pigment disk membranes 色素盤膜
visual transduction cascade 視覺級聯轉導
11-cis-retinal l 11-順-視黃醛
opsin 視蛋白
Schiff’s base Schiff’s鹼基
retinoid 視黃醇類化合物
Transducin 轉導蛋白
G-protein-coupled receptors G-蛋白偶聯受體
G-protein G-蛋白
enzyme 酶
allosteric effector 別構效應劑
sodium channel 鈉通道
sodium ions 鈉離子
Dark Current 暗電流
neurotransmitter glutamate 神經遞質穀氨酸
photoreceptor synapse 光感受器突觸
guanylate cyclase 鳥苷酸環化酶
rhodopsin 視紫紅質
subunits 亞基
phototransduction 光轉導
replenished 補充
Vitamin A 維生素A
choriocapillaris 脈絡膜毛細血管
production and shedding 生成和脫落
photosensitive pigments 光敏色素
phagocytosed 吞噬
ciliary process 睫狀突
distal tip 遠端
DOI: 10.1016/bs.pmbts.2015.06.001
Ophthalmology