During light exposure, this would makerepetitive bleaching and regener terjemahan - During light exposure, this would makerepetitive bleaching and regener Bahasa Indonesia Bagaimana mengatakan

During light exposure, this would m

During light exposure, this would make
repetitive bleaching and regeneration of rhodopsin more likely in distal ROS disks.
Another reason for light’s effects in ROS tips may be related to differences in membrane
composition. For example, a gradient of membrane cholesterol content has been found in ROS
(Andrews and Cohen, 1979; Caldwell and McLaughlin, 1985). Distal disks have a lower
cholesterol/phospholipid ratio than found in disks located near the ROS base (Boesze-Battaglia
et al., 1990; ibid1994). Because newly formed ROS disks progressively displace older ones,
the distribution of cholesterol is therefore related to disk age. This regional difference in ROS
disk sterol content can affect visual transduction. Light stimulated phosphodiesterase activity
is lower in nascent ROS disks, compared to those located in the distal region of ROS (Boesze-
Battaglia and Albert, 1990). Lower membrane cholesterol in older disks might also affect the
shedding of light damaged ROS and impact the level of lipid oxidation. Kayatz et al. (1999)
found increased peroxide reactivity in ROS upon intense light exposure, but the oxidation was
not focused exclusively in the ROS tips. Furthermore, although photo-damage in rat retina
leads to cholesterol oxidation, this occurs primarily in the RPE, rod inner segments and
ganglion cell layer (Rodriguez and Fliesler, 2009). The presence of light-induced peroxides in
ROS disks of various ages and cholesterol content suggests that ROS fatty acids are the likely
target of oxidative attack.
2.1.2 Time Course of Photoreceptor Damage and Cell Death—Rhodopsin’s
activation by intense light generates signals that initiate pathological changes in the rod
photoreceptor cell body. Although details of this signaling cascade are currently unknown, the
entire rod cell, from ROS tip to synaptic terminal, is quickly involved. The rapidity with which
this occurs suggests that a diffusible substance is the agent of damage, but this has not yet been
demonstrated. Ultimately, however, light damage leads to visual cell death through a series of
apoptotic events. One manifestation of apoptosis is the appearance of double stranded DNA
breaks, detectable as a “ladder” of 180–200 base pair fragments upon agarose gel
electrophoresis. Whereas DNA fragmentation is a relatively late apoptotic event, the onset of
DNA ladder formation in the retina begins within hours of light onset and depends on the
wavelengths of light used, as well as its intensity (Shahinfar et al., 1991; Remé et al., 1995;
Li et al., 1996). In rats, a retinal DNA ladder was detectable after several hours of green light
exposure at an intensity of about 3000 lux (Shahinfar et al., 1991; Li et al., 1996). Remé et
al. (1995) reported extensive DNA ladder formation after only 2 hours of white light exposure,
also at 3000 lux. In each case, TUNEL staining revealed the appearance of fragmented DNA
in the ONL which coincided with the presence of DNA ladders. These changes were also found
to coincide with, or be preceded by, single-strand DNA breaks (Organisciak et al., 1999a) and
nuclear chromatin condensation (Shahinfar et al., 1991; Hafezi et al., 1997a), lending support
to the hypothesis of a light-induced diffusible oxidative agent.
Knowing the relative time courses of apoptotic changes and DNA fragmentation can help
elucidate the mechanism of light damage by indicating when photoreceptor damage has tipped
to the point of initiating cell death. One problem with determining the onset of DNA damage
is detecting the low level of strand cleavage that precedes the appearance of DNA ladders, or
TUNEL reactivity. Another is the long duration of some intense light exposures, which makes
it difficult to know how much light is required to initiate visual cell death. To detect early signs of DNA fragmentation, we sought to accelerate the rate of light damage across the entire retina.
Fortunately, Werner Noell provided us with one of his original hyperthermic light exposure
chambers (Noell et al., 1966). This allowed us to treat rats for brief periods, and then to assess
the near synchronous development of DNA fragmentation occurring in practically all
photoreceptors. Figure 2 contains retinal DNA fragmentation patterns after 2 hours of green
light, under hyperthermia, followed by various times in darkness at room temperature. Elevenhundred
lux of 490–580nm light were used in these experiments because rhodopsin absorbs
maximally in that region of the spectrum. According to Gordon et al. (2002), only about one
third of white fluorescent light overlaps with rhodopsin’s absorption spectrum. This means
that our green light exposures would be nearly equivalent to 3000 lux of full spectrum white
light, but without the potential for spurious effects from short wave length, higher energy light.
As shown in Figure 2, DNA fragmentation is clearly present 4 hours after light exposure and
is most likely present after only 2 hours. DNA degradation increases thereafter, is at its
maximum 1–2 days later, and is practically absent after 4 days. This suggests that the onset of
light-induced DNA damage is rapid, occurring in about 2 hours, and that once started DNA
degradation continues for about 2 days. At that time, DNA in severely damaged photoreceptor
cells has been completely degraded and DNA repair (Gordon et al., 2002) is nearly completed
in photoreceptors destined to survive.
2.1.3 Caspases and Other Early Events—Conventional thinking suggests that, if
double-strand DNA fragmentation is endonuclease-mediated and detectable within several
hours of damaging light exposure, then enzyme activation should be preceded by identifiable
up-stream events. During apoptosis, an increase in cellular caspase activity is generally, but
not always, regarded as a precursor to DNA degradation. In the case of retinal light damage in
rats, activation of caspases-1, 3, 7, 8, and 9 has been reported to occur (Wu et al., 2002; Paterson,
2005; Perche et al., 2007). Evidence supporting the involvement of caspases in light damage
includes Western analysis of pro-caspases and their proteolytic cleavage products (Wu et al.,
2002; Patterson, 2005). Perche et al. (2007) used synthetic caspase inhibitors and found that
caspases-3 and 7 were active during a 24 hour light exposure, while caspases-1 and 4 and
calpains were active 1 day later. Increases in caspase mRNAs also occur during prolonged light
treatment (Wu et al., 2002; Patterson, 2005). Tomita et al. (2005) reported that caspase-3
mRNA was elevated in rat retina after 6–12 hours of light, but that its enzymatic activity was
unaffected. Li et al. (2003) found no increase in retinal caspase-3 protein levels upon bright
light adaptation of rats for several days and subsequent intense light treatment. Similarly,
following brief periods of intense white light, Donovan et al. (2001) found increased levels of
intracellular calcium and superoxide and mitochondrial membrane depolarization in retinal
cells from Balb/c mice, but no activation of caspase-3. Inhibition of the neuronal form of nitric
oxide synthase (NOS), prevented TUNEL reactivity in the ONL and greatly reduced the effects
of light on calcium levels, superoxide production and mitochondria membrane potential. It was
suggested that S-nitrosylation of essential cysteine residues by nitric oxide (NO) might actually
inhibit caspase activation (Donovan et al., 2001). In the rat light damage model, inhibition of
retinal NOS provided structural protection of photoreceptors, but only modest functional
protection (Kaldi et al., 2003). In rat brain neurons, NO treatment led to decreases in NADH
(Zhang et al., 1994) and ATP, changes which appear to promote necrotic cell death over
apoptosis (Leist et al., 1999).
Given the time frame of retinal DNA fragmentation and the differences noted above, at this
point only a few general conclusions are possible. First, the role of caspases in retinal light
damage appears to be animal model specific. In the rat retina, caspase-3 mRNA levels increase
rapidly during intense light and inhibition of caspase activity prevents light damage. In some
cases, caspase-3 activation precedes or is coincidental with DNA fragmentation; in others, it
does not appear to be active. It is worth noting that Tomita et al. (2005) and Perche et al.
(2007) used different strains of albino rats which may exhibit different susceptibilities to retinal light damage (Borges et al., 1990; Iseli et al., 2002). Caspase-1 activation in rats appears to
occur much later (Perche et al., 2007), or not at all (Tomita et al., 2005). In mice, caspase-1
mRNA levels increase 6–8 hours after light treatment, indicating a down-stream role in DNA
degradation (Grimm et al., 2000b). Second, calpain activity increases 1 day after the end of
light treatment in rats (Perche et al., 2007), but its activation may occur sooner in mice. Calcium
dependent calpain activation is rapid in vitro, while being inhibited by antioxidants (Sanvicens
et al., 2004). The activation of many endonucleases also depends on cellular calcium and
antioxidants are known to prevent retinal light damage. This suggests a role for both calcium
ion and oxidative stress in the damage process. In support of a role for calcium, rats treated
with Flunarizine, which blocks calcium release from intracellular stores, exhibited reduced
light damage (Edward et al., 1991). Finally, differences in the light levels required to induce
retinal damage also seem to be species specific. Mice generally require more intense light to
induce damage than rats, and different light intensity-dependent apoptotic pathways are known
to exist (Hao et al., 2002). Apoptotic cell death is an energy dependent process whereas necrosis
is affected more by cellular calcium (Yuan et al., 2003).
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During light exposure, this would makerepetitive bleaching and regeneration of rhodopsin more likely in distal ROS disks.Another reason for light’s effects in ROS tips may be related to differences in membranecomposition. For example, a gradient of membrane cholesterol content has been found in ROS(Andrews and Cohen, 1979; Caldwell and McLaughlin, 1985). Distal disks have a lowercholesterol/phospholipid ratio than found in disks located near the ROS base (Boesze-Battagliaet al., 1990; ibid1994). Because newly formed ROS disks progressively displace older ones,the distribution of cholesterol is therefore related to disk age. This regional difference in ROSdisk sterol content can affect visual transduction. Light stimulated phosphodiesterase activityis lower in nascent ROS disks, compared to those located in the distal region of ROS (Boesze-Battaglia and Albert, 1990). Lower membrane cholesterol in older disks might also affect theshedding of light damaged ROS and impact the level of lipid oxidation. Kayatz et al. (1999)found increased peroxide reactivity in ROS upon intense light exposure, but the oxidation wasnot focused exclusively in the ROS tips. Furthermore, although photo-damage in rat retinaleads to cholesterol oxidation, this occurs primarily in the RPE, rod inner segments andganglion cell layer (Rodriguez and Fliesler, 2009). The presence of light-induced peroxides inROS disks of various ages and cholesterol content suggests that ROS fatty acids are the likelytarget of oxidative attack.2.1.2 Time Course of Photoreceptor Damage and Cell Death—Rhodopsin’sactivation by intense light generates signals that initiate pathological changes in the rodphotoreceptor cell body. Although details of this signaling cascade are currently unknown, theentire rod cell, from ROS tip to synaptic terminal, is quickly involved. The rapidity with whichthis occurs suggests that a diffusible substance is the agent of damage, but this has not yet beendemonstrated. Ultimately, however, light damage leads to visual cell death through a series ofapoptotic events. One manifestation of apoptosis is the appearance of double stranded DNAbreaks, detectable as a “ladder” of 180–200 base pair fragments upon agarose gelelectrophoresis. Whereas DNA fragmentation is a relatively late apoptotic event, the onset ofDNA ladder formation in the retina begins within hours of light onset and depends on thewavelengths of light used, as well as its intensity (Shahinfar et al., 1991; Remé et al., 1995;Li et al., 1996). In rats, a retinal DNA ladder was detectable after several hours of green lightexposure at an intensity of about 3000 lux (Shahinfar et al., 1991; Li et al., 1996). Remé etal. (1995) reported extensive DNA ladder formation after only 2 hours of white light exposure,also at 3000 lux. In each case, TUNEL staining revealed the appearance of fragmented DNAin the ONL which coincided with the presence of DNA ladders. These changes were also foundto coincide with, or be preceded by, single-strand DNA breaks (Organisciak et al., 1999a) andnuclear chromatin condensation (Shahinfar et al., 1991; Hafezi et al., 1997a), lending supportto the hypothesis of a light-induced diffusible oxidative agent.Knowing the relative time courses of apoptotic changes and DNA fragmentation can helpelucidate the mechanism of light damage by indicating when photoreceptor damage has tippedto the point of initiating cell death. One problem with determining the onset of DNA damageis detecting the low level of strand cleavage that precedes the appearance of DNA ladders, orTUNEL reactivity. Another is the long duration of some intense light exposures, which makesit difficult to know how much light is required to initiate visual cell death. To detect early signs of DNA fragmentation, we sought to accelerate the rate of light damage across the entire retina.Fortunately, Werner Noell provided us with one of his original hyperthermic light exposurechambers (Noell et al., 1966). This allowed us to treat rats for brief periods, and then to assessthe near synchronous development of DNA fragmentation occurring in practically allphotoreceptors. Figure 2 contains retinal DNA fragmentation patterns after 2 hours of greenlight, under hyperthermia, followed by various times in darkness at room temperature. Elevenhundredlux of 490–580nm light were used in these experiments because rhodopsin absorbsmaximally in that region of the spectrum. According to Gordon et al. (2002), only about onethird of white fluorescent light overlaps with rhodopsin’s absorption spectrum. This meansthat our green light exposures would be nearly equivalent to 3000 lux of full spectrum whitelight, but without the potential for spurious effects from short wave length, higher energy light.As shown in Figure 2, DNA fragmentation is clearly present 4 hours after light exposure andis most likely present after only 2 hours. DNA degradation increases thereafter, is at itsmaximum 1–2 days later, and is practically absent after 4 days. This suggests that the onset oflight-induced DNA damage is rapid, occurring in about 2 hours, and that once started DNAdegradation continues for about 2 days. At that time, DNA in severely damaged photoreceptorcells has been completely degraded and DNA repair (Gordon et al., 2002) is nearly completedin photoreceptors destined to survive.2.1.3 Caspases and Other Early Events—Conventional thinking suggests that, ifdouble-strand DNA fragmentation is endonuclease-mediated and detectable within severalhours of damaging light exposure, then enzyme activation should be preceded by identifiableup-stream events. During apoptosis, an increase in cellular caspase activity is generally, butnot always, regarded as a precursor to DNA degradation. In the case of retinal light damage inrats, activation of caspases-1, 3, 7, 8, and 9 has been reported to occur (Wu et al., 2002; Paterson,2005; Perche et al., 2007). Evidence supporting the involvement of caspases in light damageincludes Western analysis of pro-caspases and their proteolytic cleavage products (Wu et al.,2002; Patterson, 2005). Perche et al. (2007) used synthetic caspase inhibitors and found thatcaspases-3 and 7 were active during a 24 hour light exposure, while caspases-1 and 4 andcalpains were active 1 day later. Increases in caspase mRNAs also occur during prolonged lighttreatment (Wu et al., 2002; Patterson, 2005). Tomita et al. (2005) reported that caspase-3mRNA was elevated in rat retina after 6–12 hours of light, but that its enzymatic activity wasunaffected. Li et al. (2003) found no increase in retinal caspase-3 protein levels upon brightlight adaptation of rats for several days and subsequent intense light treatment. Similarly,following brief periods of intense white light, Donovan et al. (2001) found increased levels ofintracellular calcium and superoxide and mitochondrial membrane depolarization in retinalcells from Balb/c mice, but no activation of caspase-3. Inhibition of the neuronal form of nitricoxide synthase (NOS), prevented TUNEL reactivity in the ONL and greatly reduced the effectsof light on calcium levels, superoxide production and mitochondria membrane potential. It wassuggested that S-nitrosylation of essential cysteine residues by nitric oxide (NO) might actuallyinhibit caspase activation (Donovan et al., 2001). In the rat light damage model, inhibition ofretinal NOS provided structural protection of photoreceptors, but only modest functionalprotection (Kaldi et al., 2003). In rat brain neurons, NO treatment led to decreases in NADH(Zhang et al., 1994) and ATP, changes which appear to promote necrotic cell death overapoptosis (Leist et al., 1999).Given the time frame of retinal DNA fragmentation and the differences noted above, at thispoint only a few general conclusions are possible. First, the role of caspases in retinal lightdamage appears to be animal model specific. In the rat retina, caspase-3 mRNA levels increaserapidly during intense light and inhibition of caspase activity prevents light damage. In somecases, caspase-3 activation precedes or is coincidental with DNA fragmentation; in others, itdoes not appear to be active. It is worth noting that Tomita et al. (2005) and Perche et al.(2007) used different strains of albino rats which may exhibit different susceptibilities to retinal light damage (Borges et al., 1990; Iseli et al., 2002). Caspase-1 activation in rats appears tooccur much later (Perche et al., 2007), or not at all (Tomita et al., 2005). In mice, caspase-1mRNA levels increase 6–8 hours after light treatment, indicating a down-stream role in DNAdegradation (Grimm et al., 2000b). Second, calpain activity increases 1 day after the end oflight treatment in rats (Perche et al., 2007), but its activation may occur sooner in mice. Calciumdependent calpain activation is rapid in vitro, while being inhibited by antioxidants (Sanvicenset al., 2004). The activation of many endonucleases also depends on cellular calcium andantioxidants are known to prevent retinal light damage. This suggests a role for both calciumion and oxidative stress in the damage process. In support of a role for calcium, rats treatedwith Flunarizine, which blocks calcium release from intracellular stores, exhibited reducedlight damage (Edward et al., 1991). Finally, differences in the light levels required to induceretinal damage also seem to be species specific. Mice generally require more intense light toinduce damage than rats, and different light intensity-dependent apoptotic pathways are knownto exist (Hao et al., 2002). Apoptotic cell death is an energy dependent process whereas necrosisis affected more by cellular calcium (Yuan et al., 2003).
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Saat terpapar cahaya, ini akan membuat
pemutihan berulang-ulang dan regenerasi rhodopsin lebih mungkin terjadi pada disk ROS distal.
Alasan lain untuk efek cahaya di ujung ROS mungkin berkaitan dengan perbedaan dalam membran
komposisi. Misalnya, gradien konten membran kolesterol telah ditemukan di ROS
(Andrews dan Cohen, 1979; Caldwell dan McLaughlin, 1985). Disk distal memiliki lebih rendah
rasio kolesterol / fosfolipid daripada yang ditemukan di disk terletak di dekat pangkalan ROS (Boesze-Battaglia
et al, 1990;. ibid1994). Karena baru dibentuk disk ROS semakin menggantikan yang lebih tua,
distribusi kolesterol karena itu terkait dengan usia disk. Perbedaan regional di ROS
konten disk yang sterol dapat mempengaruhi transduksi visual. Cahaya menstimulasi aktivitas phosphodiesterase
lebih rendah pada disk ROS baru lahir, dibandingkan dengan mereka yang berada di wilayah distal dari ROS (Boesze-
Battaglia dan Albert, 1990). Kolesterol membran yang lebih rendah dalam disk yang lebih tua mungkin juga mempengaruhi
penumpahan cahaya yang rusak ROS dan mempengaruhi tingkat oksidasi lipid. Kayatz et al. (1999)
menemukan peningkatan reaktivitas peroksida di ROS setelah terpapar cahaya yang kuat, namun oksidasi itu
tidak terfokus hanya pada tips ROS. Selain itu, meskipun foto-kerusakan di retina tikus
menyebabkan oksidasi kolesterol, ini terjadi terutama di RPE, segmen dalam batang dan
lapisan sel ganglion (Rodriguez dan Fliesler, 2009). Kehadiran peroksida cahaya yang disebabkan di
ROS disk dari berbagai usia dan kadar kolesterol menunjukkan bahwa asam lemak ROS adalah kemungkinan
target serangan oksidatif.
2.1.2 Waktu Kursus fotoreseptor Kerusakan dan Cell Death-Rhodopsin itu
aktivasi dengan cahaya yang kuat menghasilkan sinyal yang memulai perubahan patologis di batang
sel tubuh fotoreseptor. Meskipun rincian dari kaskade sinyal ini saat ini tidak diketahui, yang
seluruh sel batang, dari ROS ujung ke terminal sinaptik, dengan cepat terlibat. Kecepatan dengan
ini terjadi menunjukkan bahwa zat diffusible adalah agen kerusakan, tetapi hal ini belum
dibuktikan. Pada akhirnya, bagaimanapun, kerusakan ringan menyebabkan kematian sel visual melalui serangkaian
peristiwa apoptosis. Salah satu manifestasi dari apoptosis adalah munculnya ganda DNA beruntai
istirahat, terdeteksi sebagai "tangga" dari 180-200 fragmen pasangan basa pada gel agarose
elektroforesis. Sedangkan fragmentasi DNA adalah peristiwa relatif terlambat apoptosis, awal
pembentukan tangga DNA di retina dimulai beberapa jam setelah onset cahaya dan tergantung pada
panjang gelombang cahaya yang digunakan, serta intensitasnya (Shahinfar et al, 1991;. reme et al ., 1995;
Li et al, 1996).. Pada tikus, tangga DNA retina terdeteksi setelah beberapa jam lampu hijau
paparan pada intensitas sekitar 3000 lux (Shahinfar et al, 1991;.. Li et al, 1996). Reme et
al. (1995) melaporkan pembentukan tangga DNA luas setelah hanya 2 jam dari paparan cahaya putih,
juga pada 3000 lux. Dalam setiap kasus, TUNEL pewarnaan mengungkapkan penampilan DNA terfragmentasi
di ONL yang bertepatan dengan kehadiran tangga DNA. Perubahan ini juga ditemukan
bertepatan dengan, atau didahului oleh, istirahat DNA untai tunggal dan (Organisciak et al, 1999a.)
kromatin nuklir kondensasi (Shahinfar et al, 1991;. Hafezi et al, 1997a.), memberikan dukungan
untuk hipotesis dari agen oksidatif ringan yang disebabkan diffusible.
Mengetahui kursus waktu relatif perubahan apoptosis dan fragmentasi DNA dapat membantu
menjelaskan mekanisme kerusakan ringan dengan menunjukkan ketika kerusakan fotoreseptor telah berujung
ke titik memulai kematian sel. Satu masalah dengan menentukan timbulnya kerusakan DNA
mendeteksi tingkat rendah untai pembelahan yang mendahului munculnya tangga DNA, atau
TUNEL reaktivitas. Lain adalah durasi panjang beberapa eksposur cahaya yang kuat, yang membuatnya
sulit untuk mengetahui seberapa banyak cahaya yang diperlukan untuk memulai kematian sel visual. Untuk mendeteksi tanda-tanda awal fragmentasi DNA, kami berusaha untuk mempercepat laju kerusakan ringan di seluruh retina.
Untungnya, Werner Noell memberikan kita dengan salah satu Hyperthermic paparan cahaya aslinya
ruang (Noell et al., 1966). Hal ini memungkinkan kami untuk mengobati tikus untuk periode singkat, dan kemudian untuk menilai
perkembangan sinkron dekat fragmentasi DNA terjadi di hampir semua
fotoreseptor. Gambar 2 berisi pola fragmentasi DNA retina setelah 2 jam hijau
terang, di bawah hipertermia, diikuti oleh berbagai kali dalam kegelapan pada suhu kamar. Elevenhundred
lux cahaya 490-580nm yang digunakan dalam percobaan ini karena rhodopsin menyerap
secara maksimal dalam wilayah spektrum. Menurut Gordon et al. (2002), hanya sekitar satu
sepertiga dari lampu neon putih tumpang tindih dengan spektrum penyerapan rhodopsin itu. Ini berarti
bahwa eksposur lampu hijau kami akan hampir setara dengan 3000 lux putih spektrum penuh
cahaya, tapi tanpa potensi efek palsu dari panjang gelombang pendek, cahaya energi yang lebih tinggi.
Seperti ditunjukkan dalam Gambar 2, fragmentasi DNA jelas hadir 4 jam setelah paparan cahaya dan
kemungkinan besar hadir setelah hanya 2 jam. Degradasi DNA meningkat setelah itu, berada pada titik
maksimum 1-2 hari kemudian, dan praktis tidak ada setelah 4 hari. Hal ini menunjukkan bahwa terjadinya
kerusakan DNA cahaya yang disebabkan cepat, terjadi di sekitar 2 jam, dan bahwa DNA sekali dimulai
degradasi terus selama sekitar 2 hari. Pada saat itu, DNA di fotoreseptor yang rusak parah
sel telah benar-benar terdegradasi dan perbaikan DNA (Gordon et al., 2002) hampir selesai
dalam fotoreseptor ditakdirkan untuk bertahan hidup.
2.1.3 caspases dan Awal Acara-konvensional pemikiran lain menunjukkan bahwa, jika
ganda -strand fragmentasi DNA adalah endonuklease-dimediasi dan terdeteksi dalam beberapa
jam penyinaran merusak, maka enzim aktivasi harus didahului oleh diidentifikasi
peristiwa up-stream. Selama apoptosis, peningkatan aktivitas caspase seluler umumnya, tapi
tidak selalu, dianggap sebagai pendahulu untuk degradasi DNA. Dalam kasus kerusakan retina cahaya dalam
tikus, aktivasi caspases-1, 3, 7, 8, dan 9 telah dilaporkan terjadi (Wu et al, 2002;. Paterson,
2005; Perche et al, 2007.). Bukti yang mendukung keterlibatan caspases kerusakan ringan
meliputi analisis Western pro-caspases dan produk pembelahan proteolitik mereka (Wu et al,.
2002; Patterson, 2005). Perche et al. (2007) menggunakan inhibitor caspase sintetis dan menemukan bahwa
caspases-3 dan 7 aktif selama 24 jam paparan cahaya, sementara caspases-1 dan 4 dan
Calpain aktif 1 hari kemudian. Peningkatan mRNA caspase juga terjadi selama cahaya berkepanjangan
pengobatan (Wu et al, 2002;. Patterson, 2005). Tomita et al. (2005) melaporkan bahwa caspase-3
mRNA meningkat pada tikus retina setelah 6-12 jam cahaya, tetapi aktivitas enzimatik yang sangat
terpengaruh. Li et al. (2003) tidak menemukan peningkatan retina caspase-3 tingkat protein pada terang
adaptasi cahaya tikus selama beberapa hari dan pengobatan cahaya yang kuat berikutnya. Demikian pula,
setelah periode singkat cahaya putih yang kuat, Donovan et al. (2001) menemukan peningkatan kadar
kalsium intraseluler dan superoksida dan mitokondria membran depolarisasi di retina
sel dari tikus Balb / c, tapi tidak ada aktivasi caspase-3. Penghambatan bentuk neuronal nitrat
oksida sintase (NOS), mencegah TUNEL reaktivitas di ONL dan sangat mengurangi efek
cahaya pada kadar kalsium, produksi superoksida dan potensi membran mitokondria. Itu
menunjukkan bahwa S-nitrosylation residu sistein penting oleh oksida nitrat (NO) mungkin sebenarnya
menghambat aktivasi caspase (Donovan et al., 2001). Dalam model kerusakan ringan tikus, penghambatan
retina NOS memberikan perlindungan struktural fotoreseptor, tetapi hanya fungsional sederhana
perlindungan (Kaldi et al., 2003). Dalam neuron otak tikus, NO pengobatan menyebabkan penurunan NADH
(Zhang et al., 1994) dan ATP, perubahan yang muncul untuk mempromosikan kematian sel nekrotik selama
apoptosis (Leist et al., 1999).
Mengingat jangka waktu fragmentasi DNA retina dan perbedaan yang disebutkan di atas, di
titik hanya beberapa kesimpulan umum yang mungkin. Pertama, peran caspases dalam cahaya retina
kerusakan tampaknya model hewan tertentu. Di retina tikus, caspase-3 tingkat mRNA meningkat
pesat selama cahaya yang kuat dan penghambatan aktivitas caspase mencegah kerusakan ringan. Dalam beberapa
kasus, aktivasi caspase-3 mendahului atau kebetulan dengan fragmentasi DNA; pada orang lain, itu
tidak muncul untuk menjadi aktif. Perlu dicatat bahwa Tomita et al. . (2005) dan Perche et al
(2007) menggunakan strain yang berbeda dari tikus albino yang mungkin menunjukkan kerentanan yang berbeda untuk kerusakan ringan retina (Borges et al, 1990;. Iseli et al., 2002). Caspase-1 aktivasi pada tikus tampaknya
terjadi banyak kemudian (Perche et al., 2007), atau tidak sama sekali (Tomita et al., 2005). Pada tikus, caspase-1
tingkat mRNA meningkat 6-8 jam setelah perawatan ringan, yang menunjukkan peran hilir dalam DNA
degradasi (Grimm et al., 2000b). Kedua, aktivitas calpain meningkat 1 hari setelah akhir
perawatan ringan pada tikus (Perche et al., 2007), tetapi aktivasi dapat terjadi lebih cepat pada tikus. Kalsium
tergantung aktivasi calpain yang cepat in vitro, sedangkan yang dihambat oleh antioksidan (Sanvicens
et al., 2004). Aktivasi banyak endonuklease juga tergantung pada kalsium seluler dan
antioksidan yang dikenal untuk mencegah kerusakan ringan retina. Ini menunjukkan peran untuk kedua kalsium
ion dan stres oksidatif dalam proses kerusakan. Untuk mendukung peran kalsium, tikus diobati
dengan flunarizine, yang menghambat pelepasan kalsium dari toko intraseluler, dipamerkan mengurangi
kerusakan ringan (Edward et al., 1991). Akhirnya, perbedaan dalam tingkat cahaya yang diperlukan untuk menginduksi
kerusakan retina juga tampaknya menjadi spesies tertentu. Tikus umumnya membutuhkan cahaya yang lebih intens untuk
menginduksi kerusakan daripada tikus, dan tergantung intensitas jalur apoptosis cahaya yang berbeda diketahui
ada (Hao et al., 2002). Apoptosis adalah proses tergantung energi sedangkan nekrosis
yang lebih dipengaruhi oleh kalsium seluler (Yuan et al., 2003).
Sedang diterjemahkan, harap tunggu..
 
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